International Journal of Molecular Sciences

Editorial

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3 pages, 151 KiB

Open AccessEditorial

Special Issue on Advances in Molecular Simulation

by Małgorzta Borówko

Int. J. Mol. Sci. 2021, 22(22), 12484; https://doi.org/10.3390/ijms222212484 - 19 Nov 2021

Cited by 1 | Viewed by 1729

Abstract

Rapid advances are taking place in the application of molecular simulations to study complex systems [...] Full article

(This article belongs to the Special Issue Advances in Molecular Simulation)

Research

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25 pages, 13052 KiB

Open AccessArticle

Simu-D: A Simulator-Descriptor Suite for Polymer-Based Systems under Extreme Conditions

by Miguel Herranz, Daniel Martínez-Fernández, Pablo Miguel Ramos, Katerina Foteinopoulou, Nikos Ch. Karayiannis and Manuel Laso

Int. J. Mol. Sci. 2021, 22(22), 12464; https://doi.org/10.3390/ijms222212464 - 18 Nov 2021

Cited by 10 | Viewed by 2392

Abstract

We present Simu-D, a software suite for the simulation and successive identification of local structures of atomistic systems, based on polymers, under extreme conditions, in the bulk, on surfaces, and at interfaces. The protocol is built around various types of Monte Carlo algorithms, [...] Read more.

We present Simu-D, a software suite for the simulation and successive identification of local structures of atomistic systems, based on polymers, under extreme conditions, in the bulk, on surfaces, and at interfaces. The protocol is built around various types of Monte Carlo algorithms, which include localized, chain-connectivity-altering, identity-exchange, and cluster-based moves. The approach focuses on alleviating one of the main disadvantages of Monte Carlo algorithms, which is the general applicability under a wide range of conditions. Present applications include polymer-based nanocomposites with nanofillers in the form of cylinders and spheres of varied concentration and size, extremely confined and maximally packed assemblies in two and three dimensions, and terminally grafted macromolecules. The main simulator is accompanied by a descriptor that identifies the similarity of computer-generated configurations with respect to reference crystals in two or three dimensions. The Simu-D simulator-descriptor can be an especially useful tool in the modeling studies of the entropy- and energy-driven phase transition, adsorption, and self-organization of polymer-based systems under a variety of conditions. Full article

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17 pages, 4217 KiB

Open AccessArticle

Structural and Dynamical Behaviour of Colloids with Competing Interactions Confined in Slit Pores

by Horacio Serna, Wojciech T. Góźdź and Eva G. Noya

Int. J. Mol. Sci. 2021, 22(20), 11050; https://doi.org/10.3390/ijms222011050 - 13 Oct 2021

Cited by 3 | Viewed by 2013

Abstract

Systems with short-range attractive and long-range repulsive interactions can form periodic modulated phases at low temperatures, such as cluster-crystal, hexagonal, lamellar and bicontinuous gyroid phases. These periodic microphases should be stable regardless of the physical origin of the interactions. However, they have not [...] Read more.

Systems with short-range attractive and long-range repulsive interactions can form periodic modulated phases at low temperatures, such as cluster-crystal, hexagonal, lamellar and bicontinuous gyroid phases. These periodic microphases should be stable regardless of the physical origin of the interactions. However, they have not yet been experimentally observed in colloidal systems, where, in principle, the interactions can be tuned by modifying the colloidal solution. Our goal is to investigate whether the formation of some of these periodic microphases can be promoted by confinement in narrow slit pores. By performing simulations of a simple model with competing interactions, we find that both the cluster-crystal and lamellar phases can be stable up to higher temperatures than in the bulk system, whereas the hexagonal phase is destabilised at temperatures somewhat lower than in bulk. Besides, we observed that the internal ordering of the lamellar phase can be modified by changing the pore width. Interestingly, for sufficiently wide pores to host three lamellae, there is a range of temperatures for which the two lamellae close to the walls are internally ordered, whereas the one at the centre of the pore remains internally disordered. We also find that particle diffusion under confinement exhibits a complex dependence with the pore width and with the density, obtaining larger and smaller values of the diffusion coefficient than in the corresponding bulk system. Full article

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16 pages, 5353 KiB

Open AccessArticle

A Systematic Approach: Molecular Dynamics Study and Parametrisation of Gemini Type Cationic Surfactants

by Mateusz Rzycki, Aleksandra Kaczorowska, Sebastian Kraszewski and Dominik Drabik

Int. J. Mol. Sci. 2021, 22(20), 10939; https://doi.org/10.3390/ijms222010939 - 10 Oct 2021

Cited by 4 | Viewed by 2541

Abstract

The spreading of antibiotic-resistant bacteria strains is one of the most serious problem in medicine to struggle nowadays. This triggered the development of alternative antimicrobial agents in recent years. One of such group is Gemini surfactants which are massively synthesised in various structural [...] Read more.

The spreading of antibiotic-resistant bacteria strains is one of the most serious problem in medicine to struggle nowadays. This triggered the development of alternative antimicrobial agents in recent years. One of such group is Gemini surfactants which are massively synthesised in various structural configurations to obtain the most effective antibacterial properties. Unfortunately, the comparison of antimicrobial effectiveness among different types of Gemini agents is unfeasible since various protocols for the determination of Minimum Inhibitory Concentration are used. In this work, we proposed alternative, computational, approach for such comparison. We designed a comprehensive database of 250 Gemini surfactants. Description of structure parameters, for instance spacer type and length, are included in the database. We parametrised modelled molecules to obtain force fields for the entire Gemini database. This was used to conduct in silico studies using the molecular dynamics to investigate the incorporation of these agents into model E. coli inner membrane system. We evaluated the effect of Gemini surfactants on structural, stress and mechanical parameters of the membrane after the agent incorporation. This enabled us to select four most likely membrane properties that could correspond to Gemini’s antimicrobial effect. Based on our results we selected several types of Gemini spacers which could demonstrate a particularly strong effect on the bacterial membranes. Full article

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18 pages, 1359 KiB

Open AccessArticle

Phase Transitions in Two-Dimensional Systems of Janus-like Particles on a Triangular Lattice

by Andrzej Patrykiejew

Int. J. Mol. Sci. 2021, 22(19), 10484; https://doi.org/10.3390/ijms221910484 - 28 Sep 2021

Cited by 2 | Viewed by 1530

Abstract

We studied the phase behavior of two-dimensional systems of Janus-like particles on a triangular lattice using Monte Carlo methods. The model assumes that each particle can take on one of the six orientations with respect to the lattice, and the interactions between neighboring [...] Read more.

We studied the phase behavior of two-dimensional systems of Janus-like particles on a triangular lattice using Monte Carlo methods. The model assumes that each particle can take on one of the six orientations with respect to the lattice, and the interactions between neighboring particles were weighted depending on the degree to which their A and B halves overlap. In this work, we assumed that the AA interaction was fixed and attractive, while the AB and BB interactions varied. We demonstrated that the phase behavior of the systems considered strongly depended on the magnitude of the interaction energies between the AB and BB halves. Here, we considered systems with non-repulsive interactions only and determined phase diagrams for several systems. We demonstrated that the phase diagram topology depends on the temperature at which the close-packed systems undergo the orientational order–disorder transition. Full article

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16 pages, 1939 KiB

Open AccessArticle

Can We Predict the Isosymmetric Phase Transition? Application of DFT Calculations to Study the Pressure Induced Transformation of Chlorothiazide

by Łukasz Szeleszczuk, Anna Helena Mazurek, Katarzyna Milcarz, Ewa Napiórkowska and Dariusz Maciej Pisklak

Int. J. Mol. Sci. 2021, 22(18), 10100; https://doi.org/10.3390/ijms221810100 - 18 Sep 2021

Cited by 4 | Viewed by 2996

Abstract

Isosymmetric structural phase transition (IPT, type 0), in which there are no changes in the occupation of Wyckoff positions, the number of atoms in the unit cell, and the space group symmetry, is relatively uncommon. Chlorothiazide, a diuretic agent with a secondary function [...] Read more.

Isosymmetric structural phase transition (IPT, type 0), in which there are no changes in the occupation of Wyckoff positions, the number of atoms in the unit cell, and the space group symmetry, is relatively uncommon. Chlorothiazide, a diuretic agent with a secondary function as an antihypertensive, has been proven to undergo pressure-induced IPT of Form I to Form II at 4.2 GPa. For that reason, it has been chosen as a model compound in this study to determine if IPT can be predicted in silico using periodic DFT calculations. The transformation of Form II into Form I, occurring under decompression, was observed in geometry optimization calculations. However, the reverse transition was not detected, although the calculated differences in the DFT energies and thermodynamic parameters indicated that Form II should be more stable at increased pressure. Finally, the IPT was successfully simulated using ab initio molecular dynamics calculations. Full article

(This article belongs to the Special Issue Advances in Molecular Simulation)

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13 pages, 2120 KiB

Open AccessArticle

Exploring the Binding Mechanism of PF-07321332 SARS-CoV-2 Protease Inhibitor through Molecular Dynamics and Binding Free Energy Simulations

by Bilal Ahmad, Maria Batool, Qurat ul Ain, Moon Suk Kim and Sangdun Choi

Int. J. Mol. Sci. 2021, 22(17), 9124; https://doi.org/10.3390/ijms22179124 - 24 Aug 2021

Cited by 91 | Viewed by 11985

Abstract

The novel coronavirus disease, caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), rapidly spreading around the world, poses a major threat to the global public health. Herein, we demonstrated the binding mechanism of PF-07321332, α-ketoamide, lopinavir, and ritonavir to the coronavirus 3-chymotrypsin-like-protease (3CL [...] Read more.

The novel coronavirus disease, caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), rapidly spreading around the world, poses a major threat to the global public health. Herein, we demonstrated the binding mechanism of PF-07321332, α-ketoamide, lopinavir, and ritonavir to the coronavirus 3-chymotrypsin-like-protease (3CL^pro) by means of docking and molecular dynamic (MD) simulations. The analysis of MD trajectories of 3CL^pro with PF-07321332, α-ketoamide, lopinavir, and ritonavir revealed that 3CL^pro–PF-07321332 and 3CL^pro–α-ketoamide complexes remained stable compared with 3CL^pro–ritonavir and 3CL^pro–lopinavir. Investigating the dynamic behavior of ligand–protein interaction, ligands PF-07321332 and α-ketoamide showed stronger bonding via making interactions with catalytic dyad residues His41–Cys145 of 3CL^pro. Lopinavir and ritonavir were unable to disrupt the catalytic dyad, as illustrated by increased bond length during the MD simulation. To decipher the ligand binding mode and affinity, ligand interactions with SARS-CoV-2 proteases and binding energy were calculated. The binding energy of the bespoke antiviral PF-07321332 clinical candidate was two times higher than that of α-ketoamide and three times than that of lopinavir and ritonavir. Our study elucidated in detail the binding mechanism of the potent PF-07321332 to 3CL^pro along with the low potency of lopinavir and ritonavir due to weak binding affinity demonstrated by the binding energy data. This study will be helpful for the development and optimization of more specific compounds to combat coronavirus disease. Full article

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21 pages, 18290 KiB

Open AccessArticle

Adsorption on Ligand-Tethered Nanoparticles

by Małgorzata Borówko and Tomasz Staszewski

Int. J. Mol. Sci. 2021, 22(16), 8810; https://doi.org/10.3390/ijms22168810 - 16 Aug 2021

Cited by 7 | Viewed by 2110

Abstract

We use coarse-grained molecular dynamics simulations to study adsorption on ligand-tethered particles. Nanoparticles with attached flexible and stiff ligands are considered. We discuss how the excess adsorption isotherm, the thickness of the polymer corona, and its morphology depend on the number of ligands, [...] Read more.

We use coarse-grained molecular dynamics simulations to study adsorption on ligand-tethered particles. Nanoparticles with attached flexible and stiff ligands are considered. We discuss how the excess adsorption isotherm, the thickness of the polymer corona, and its morphology depend on the number of ligands, their length, the size of the core, and the interaction parameters. We investigate the adsorption-induced structural transitions of polymer coatings. The behavior of systems involving curved and flat “brushes” is compared. Full article

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12 pages, 1021 KiB

Open AccessArticle

Time-Dependent Unitary Transformation Method in the Strong-Field-Ionization Regime with the Kramers-Henneberger Picture

by Je-Hoi Mun, Hirofumi Sakai and Dong-Eon Kim

Int. J. Mol. Sci. 2021, 22(16), 8514; https://doi.org/10.3390/ijms22168514 - 7 Aug 2021

Cited by 2 | Viewed by 2339

Abstract

Time evolution operators of a strongly ionizing medium are calculated by a time-dependent unitary transformation (TDUT) method. The TDUT method has been employed in a quantum mechanical system composed of discrete states. This method is especially helpful for solving molecular rotational dynamics in [...] Read more.

Time evolution operators of a strongly ionizing medium are calculated by a time-dependent unitary transformation (TDUT) method. The TDUT method has been employed in a quantum mechanical system composed of discrete states. This method is especially helpful for solving molecular rotational dynamics in quasi-adiabatic regimes because the strict unitary nature of the propagation operator allows us to set the temporal step size to large; a tight limitation on the temporal step size (

δ t < < 1

) can be circumvented by the strict unitary nature. On the other hand, in a strongly ionizing system where the Hamiltonian is not Hermitian, the same approach cannot be directly applied because it is demanding to define a set of field-dressed eigenstates. In this study, the TDUT method was applied to the ionizing regime using the Kramers-Henneberger frame, in which the strong-field-dressed discrete eigenstates are given by the field-free discrete eigenstates in a moving frame. Although the present work verifies the method for a one-dimensional atom as a prototype, the method can be applied to three-dimensional atoms, and molecules exposed to strong laser fields. Full article

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11 pages, 3648 KiB

Open AccessArticle

Molecular Insight into the Possible Mechanism of Drag Reduction of Surfactant Aqueous Solution in Pipe Flow

by Yusei Kobayashi, Hirotaka Gomyo and Noriyoshi Arai

Int. J. Mol. Sci. 2021, 22(14), 7573; https://doi.org/10.3390/ijms22147573 - 15 Jul 2021

Cited by 8 | Viewed by 2362

Abstract

The phenomenon of drag reduction (known as the “Toms effect”) has many industrial and engineering applications, but a definitive molecular-level theory has not yet been constructed. This is due both to the multiscale nature of complex fluids and to the difficulty of directly [...] Read more.

The phenomenon of drag reduction (known as the “Toms effect”) has many industrial and engineering applications, but a definitive molecular-level theory has not yet been constructed. This is due both to the multiscale nature of complex fluids and to the difficulty of directly observing self-assembled structures in nonequilibrium states. On the basis of a large-scale coarse-grained molecular simulation that we conducted, we propose a possible mechanism of turbulence suppression in surfactant aqueous solution. We demonstrate that maintaining sufficiently large micellar structures and a homogeneous radial distribution of surfactant molecules is necessary to obtain the drag-reduction effect. This is the first molecular-simulation evidence that a micellar structure is responsible for drag reduction in pipe flow, and should help in understanding the mechanisms underlying drag reduction by surfactant molecules under nonequilibrium conditions. Full article

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22 pages, 4803 KiB

Open AccessArticle

Recent Developments on gMicroMC: Transport Simulations of Proton and Heavy Ions and Concurrent Transport of Radicals and DNA

by Youfang Lai, Xun Jia and Yujie Chi

Int. J. Mol. Sci. 2021, 22(12), 6615; https://doi.org/10.3390/ijms22126615 - 21 Jun 2021

Cited by 6 | Viewed by 2687

Abstract

Mechanistic Monte Carlo (MC) simulation of radiation interaction with water and DNA is important for the understanding of biological responses induced by ionizing radiation. In our previous work, we employed the Graphical Processing Unit (GPU)-based parallel computing technique to develop a novel, highly [...] Read more.

Mechanistic Monte Carlo (MC) simulation of radiation interaction with water and DNA is important for the understanding of biological responses induced by ionizing radiation. In our previous work, we employed the Graphical Processing Unit (GPU)-based parallel computing technique to develop a novel, highly efficient, and open-source MC simulation tool, gMicroMC, for simulating electron-induced DNA damages. In this work, we reported two new developments in gMicroMC: the transport simulation of protons and heavy ions and the concurrent transport of radicals in the presence of DNA. We modeled these transports based on electromagnetic interactions between charged particles and water molecules and the chemical reactions between radicals and DNA molecules. Various physical properties, such as Linear Energy Transfer (LET) and particle range, from our simulation agreed with data published by NIST or simulation results from other CPU-based MC packages. The simulation results of DNA damage under the concurrent transport of radicals and DNA agreed with those from nBio-Topas simulation in a comprehensive testing case. GPU parallel computing enabled high computational efficiency. It took 41 s to simultaneously transport 100 protons with an initial kinetic energy of 10 MeV in water and 470 s to transport 10

^{5}

radicals up to 1 µs in the presence of DNA. Full article

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17 pages, 2473 KiB

Open AccessArticle

Computational-Driven Epitope Verification and Affinity Maturation of TLR4-Targeting Antibodies

by Bilal Ahmad, Maria Batool, Moon-Suk Kim and Sangdun Choi

Int. J. Mol. Sci. 2021, 22(11), 5989; https://doi.org/10.3390/ijms22115989 - 1 Jun 2021

Cited by 7 | Viewed by 3543

Abstract

Toll-like receptor (TLR) signaling plays a critical role in the induction and progression of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, experimental autoimmune encephalitis, type 1 diabetes mellitus and neurodegenerative diseases. Deciphering antigen recognition by antibodies provides insights and defines the [...] Read more.

Toll-like receptor (TLR) signaling plays a critical role in the induction and progression of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, experimental autoimmune encephalitis, type 1 diabetes mellitus and neurodegenerative diseases. Deciphering antigen recognition by antibodies provides insights and defines the mechanism of action into the progression of immune responses. Multiple strategies, including phage display and hybridoma technologies, have been used to enhance the affinity of antibodies for their respective epitopes. Here, we investigate the TLR4 antibody-binding epitope by computational-driven approach. We demonstrate that three important residues, i.e., Y328, N329, and K349 of TLR4 antibody binding epitope identified upon in silico mutagenesis, affect not only the interaction and binding affinity of antibody but also influence the structural integrity of TLR4. Furthermore, we predict a novel epitope at the TLR4-MD2 interface which can be targeted and explored for therapeutic antibodies and small molecules. This technique provides an in-depth insight into antibody–antigen interactions at the resolution and will be beneficial for the development of new monoclonal antibodies. Computational techniques, if coupled with experimental methods, will shorten the duration of rational design and development of antibody therapeutics. Full article

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19 pages, 29719 KiB

Open AccessArticle

Simple Models to Study Spectral Properties of Microbial and Animal Rhodopsins: Evaluation of the Electrostatic Effect of Charged and Polar Residues on the First Absorption Band Maxima

by Andrey A. Shtyrov, Dmitrii M. Nikolaev, Vladimir N. Mironov, Andrey V. Vasin, Maxim S. Panov, Yuri S. Tveryanovich and Mikhail N. Ryazantsev

Int. J. Mol. Sci. 2021, 22(6), 3029; https://doi.org/10.3390/ijms22063029 - 16 Mar 2021

Cited by 13 | Viewed by 3177

Abstract

A typical feature of proteins from the rhodopsin family is the sensitivity of their absorption band maximum to protein amino acid composition. For this reason, studies of these proteins often require methodologies that determine spectral shift caused by amino acid substitutions. Generally, quantum [...] Read more.

A typical feature of proteins from the rhodopsin family is the sensitivity of their absorption band maximum to protein amino acid composition. For this reason, studies of these proteins often require methodologies that determine spectral shift caused by amino acid substitutions. Generally, quantum mechanics/molecular mechanics models allow for the calculation of a substitution-induced spectral shift with high accuracy, but their application is not always easy and requires special knowledge. In the present study, we propose simple models that allow us to estimate the direct effect of a charged or polar residue substitution without extensive calculations using only rhodopsin three-dimensional structure and plots or tables that are provided in this article. The models are based on absorption maximum values calculated at the SORCI+Q level of theory for cis- and trans-forms of retinal protonated Schiff base in an external electrostatic field of charges and dipoles. Each value corresponds to a certain position of a charged or polar residue relative to the retinal chromophore. The proposed approach was evaluated against an example set consisting of twelve bovine rhodopsin and sodium pumping rhodopsin mutants. The limits of the applicability of the models are also discussed. The results of our study can be useful for the interpretation of experimental data and for the rational design of rhodopsins with required spectral properties. Full article

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24 pages, 65005 KiB

Open AccessArticle

Osmosis-Driven Water Transport through a Nanochannel: A Molecular Dynamics Simulation Study

by Changsun Eun

Int. J. Mol. Sci. 2020, 21(21), 8030; https://doi.org/10.3390/ijms21218030 - 28 Oct 2020

Cited by 3 | Viewed by 2468

Abstract

In this work, we study a chemical method to transfer water molecules from a nanoscale compartment to another initially empty compartment through a nanochannel. Without any external force, water molecules do not spontaneously move to the empty compartment because of the energy barrier [...] Read more.

In this work, we study a chemical method to transfer water molecules from a nanoscale compartment to another initially empty compartment through a nanochannel. Without any external force, water molecules do not spontaneously move to the empty compartment because of the energy barrier for breaking water hydrogen bonds in the transport process and the attraction between water molecules and the compartment walls. To overcome the energy barrier, we put osmolytes into the empty compartment, and to remove the attraction, we weaken the compartment-water interaction. This allows water molecules to spontaneously move to the empty compartment. We find that the initiation and time-transient behavior of water transport depend on the properties of the osmolytes specified by their number and the strength of their interaction with water. Interestingly, when osmolytes strongly interact with water molecules, transport immediately starts and continues until all water molecules are transferred to the initially empty compartment. However, when the osmolyte interaction strength is intermediate, transport initiates stochastically, depending on the number of osmolytes. Surprisingly, because of strong water-water interactions, osmosis-driven water transport through a nanochannel is similar to pulling a string at a constant speed. Our study helps us understand what minimal conditions are needed for complete transfer of water molecules to another compartment through a nanochannel, which may be of general concern in many fields involving molecular transfer. Full article

(This article belongs to the Special Issue Advances in Molecular Simulation)

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14 pages, 2262 KiB

Open AccessReview

Biomolecular Simulations with the Three-Dimensional Reference Interaction Site Model with the Kovalenko-Hirata Closure Molecular Solvation Theory

by Dipankar Roy and Andriy Kovalenko

Int. J. Mol. Sci. 2021, 22(10), 5061; https://doi.org/10.3390/ijms22105061 - 11 May 2021

Cited by 13 | Viewed by 3534

Abstract

The statistical mechanics-based 3-dimensional reference interaction site model with the Kovalenko-Hirata closure (3D-RISM-KH) molecular solvation theory has proven to be an essential part of a multiscale modeling framework, covering a vast region of molecular simulation techniques. The successful application ranges from the small [...] Read more.

The statistical mechanics-based 3-dimensional reference interaction site model with the Kovalenko-Hirata closure (3D-RISM-KH) molecular solvation theory has proven to be an essential part of a multiscale modeling framework, covering a vast region of molecular simulation techniques. The successful application ranges from the small molecule solvation energy to the bulk phase behavior of polymers, macromolecules, etc. The 3D-RISM-KH successfully predicts and explains the molecular mechanisms of self-assembly and aggregation of proteins and peptides related to neurodegeneration, protein-ligand binding, and structure-function related solvation properties. Upon coupling the 3D-RISM-KH theory with a novel multiple time-step molecular dynamic (MD) of the solute biomolecule stabilized by the optimized isokinetic Nosé–Hoover chain thermostat driven by effective solvation forces obtained from 3D-RISM-KH and extrapolated forward by generalized solvation force extrapolation (GSFE), gigantic outer time-steps up to picoseconds to accurately calculate equilibrium properties were obtained in this new quasidynamics protocol. The multiscale OIN/GSFE/3D-RISM-KH algorithm was implemented in the Amber package and well documented for fully flexible model of alanine dipeptide, miniprotein 1L2Y, and protein G in aqueous solution, with a solvent sampling rate ~150 times faster than a standard MD simulation in explicit water. Further acceleration in computation can be achieved by modifying the extent of solvation layers considered in the calculation, as well as by modifying existing closure relations. This enhanced simulation technique has proven applications in protein-ligand binding energy calculations, ligand/solvent binding site prediction, molecular solvation energy calculations, etc. Applications of the RISM-KH theory in molecular simulation are discussed in this work. Full article

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21 pages, 2426 KiB

Open AccessReview

“Dividing and Conquering” and “Caching” in Molecular Modeling

by Xiaoyong Cao and Pu Tian

Int. J. Mol. Sci. 2021, 22(9), 5053; https://doi.org/10.3390/ijms22095053 - 10 May 2021

Cited by 6 | Viewed by 4386

Abstract

Molecular modeling is widely utilized in subjects including but not limited to physics, chemistry, biology, materials science and engineering. Impressive progress has been made in development of theories, algorithms and software packages. To divide and conquer, and to cache intermediate results have been [...] Read more.

Molecular modeling is widely utilized in subjects including but not limited to physics, chemistry, biology, materials science and engineering. Impressive progress has been made in development of theories, algorithms and software packages. To divide and conquer, and to cache intermediate results have been long standing principles in development of algorithms. Not surprisingly, most important methodological advancements in more than half century of molecular modeling are various implementations of these two fundamental principles. In the mainstream classical computational molecular science, tremendous efforts have been invested on two lines of algorithm development. The first is coarse graining, which is to represent multiple basic particles in higher resolution modeling as a single larger and softer particle in lower resolution counterpart, with resulting force fields of partial transferability at the expense of some information loss. The second is enhanced sampling, which realizes “dividing and conquering” and/or “caching” in configurational space with focus either on reaction coordinates and collective variables as in metadynamics and related algorithms, or on the transition matrix and state discretization as in Markov state models. For this line of algorithms, spatial resolution is maintained but results are not transferable. Deep learning has been utilized to realize more efficient and accurate ways of “dividing and conquering” and “caching” along these two lines of algorithmic research. We proposed and demonstrated the local free energy landscape approach, a new framework for classical computational molecular science. This framework is based on a third class of algorithm that facilitates molecular modeling through partially transferable in resolution “caching” of distributions for local clusters of molecular degrees of freedom. Differences, connections and potential interactions among these three algorithmic directions are discussed, with the hope to stimulate development of more elegant, efficient and reliable formulations and algorithms for “dividing and conquering” and “caching” in complex molecular systems. Full article

(This article belongs to the Special Issue Advances in Molecular Simulation)

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