Folding@Home: Lessons from Eight Years of Volunteer Distributed Computing
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20 Years of Polarizable Force Field Development
20 YEARS OF POLARIZABLE FORCEFIELDDEVELOPMENTfor biomolecular systems thor van heesch Supervised by Daan P. Geerke and Paola Gori-Giorg 1 contents 2 1 Introduction 3 2contentsForce fields: Basics, Caveats and Extensions 4 2.1 The Classical Approach . 4 2.2 The caveats of point-charge electrostatics . 8 2.3 Physical phenomenon of polarizability . 10 2.4 Common implementation methods of electronic polarization . 11 2.5 Accounting for anisotropic interactions . 14 3 Knitting the reviews and perspectives together 17 3.1 Polarizability: A smoking gun? . 17 3.2 New branches of electronic polarization . 18 3.3 Descriptions of electrostatics . 19 3.4 Solvation and polarization . 20 3.5 The rise of new challenges . 21 3.6 Parameterization or polarization? . 22 3.7 Enough response: how far away? . 23 3.8 The last perspectives . 23 3.9 A new hope: the next-generation force fields . 29 4 Learning with machines 29 4.1 Replace the functional form with machine learned force fields . 31 4.2 A different take on polarizable force fields . 33 4.3 Are transferable parameters an universal requirement? . 33 4.4 The difference between derivation and prediction . 34 4.5 From small molecules to long range interactions . 36 4.6 Enough knowledge to fold a protein? . 37 4.7 Boltzmann generators, a not so hypothetical machine anymore . 38 5 Summary: The Red Thread 41 introduction 3 In this literature study we aimed to answer the following question: What has changedabstract in the outlook on polarizable force field development during the last 20 years? The theory, history, methods, and applications of polarizable force fields have been discussed to address this question. -
Using Constrained Density Functional Theory to Track Proton Transfers and to Sample Their Associated Free Energy Surface
Using Constrained Density Functional Theory to Track Proton Transfers and to Sample Their Associated Free Energy Surface Chenghan Li and Gregory A. Voth* Department of Chemistry, Chicago Center for Theoretical Chemistry, James Franck Institute, and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, 60637 Keywords: free energy sampling, proton transport, density functional theory, proton transfer ABSTRACT: The ab initio molecular dynamics (AIMD) and quantum mechanics/molecular mechanics (QM/MM) methods are powerful tools for studying proton solvation, transfer, and transport processes in various environments. However, due to the high computational cost of such methods, achieving sufficient sampling of rare events involving excess proton motion – especially when Grotthuss proton shuttling is involved – usually requires enhanced free energy sampling methods to obtain informative results. Moreover, an appropriate collective variable (CV) that describes the effective position of the net positive charge defect associated with an excess proton is essential for both tracking the trajectory of the defect and for the free energy sampling of the processes associated with the resulting proton transfer and transport. In this work, such a CV is derived from first principles using constrained density functional theory (CDFT). This CV is applicable to a broad array of proton transport and transfer processes as studied via AIMD and QM/MM simulation. 1 INTRODUCTION The accurate and efficient delineation of proton transport (PT) and -
Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development
processes Review Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development Outi M. H. Salo-Ahen 1,2,* , Ida Alanko 1,2, Rajendra Bhadane 1,2 , Alexandre M. J. J. Bonvin 3,* , Rodrigo Vargas Honorato 3, Shakhawath Hossain 4 , André H. Juffer 5 , Aleksei Kabedev 4, Maija Lahtela-Kakkonen 6, Anders Støttrup Larsen 7, Eveline Lescrinier 8 , Parthiban Marimuthu 1,2 , Muhammad Usman Mirza 8 , Ghulam Mustafa 9, Ariane Nunes-Alves 10,11,* , Tatu Pantsar 6,12, Atefeh Saadabadi 1,2 , Kalaimathy Singaravelu 13 and Michiel Vanmeert 8 1 Pharmaceutical Sciences Laboratory (Pharmacy), Åbo Akademi University, Tykistökatu 6 A, Biocity, FI-20520 Turku, Finland; ida.alanko@abo.fi (I.A.); rajendra.bhadane@abo.fi (R.B.); parthiban.marimuthu@abo.fi (P.M.); atefeh.saadabadi@abo.fi (A.S.) 2 Structural Bioinformatics Laboratory (Biochemistry), Åbo Akademi University, Tykistökatu 6 A, Biocity, FI-20520 Turku, Finland 3 Faculty of Science-Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CH Utrecht, The Netherlands; [email protected] 4 Swedish Drug Delivery Forum (SDDF), Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden; [email protected] (S.H.); [email protected] (A.K.) 5 Biocenter Oulu & Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 7 A, FI-90014 Oulu, Finland; andre.juffer@oulu.fi 6 School of Pharmacy, University of Eastern Finland, FI-70210 Kuopio, Finland; maija.lahtela-kakkonen@uef.fi (M.L.-K.); tatu.pantsar@uef.fi -
Melissa Gajewski & Jonathan Mane
Melissa Gajewski & Jonathan Mane Molecular Mechanics (MM) Methods Force fields & potential energy calculations Example using noscapine Molecular Dynamics (MD) Methods Ensembles & trajectories Example using 18-crown-6 Quantum Mechanics (QM) Methods Schrödinger’s equation Semi-empirical (SE) Wave Functional Theory (WFT) Density Functional Theory (DFT) Hybrid QM/MM & MD Methods Comparison of hybrid methods 2 3 Molecular Mechanics (MM) Methods Force fields & potential energy calculations Example using noscapine Molecular Dynamics (MD) Methods Ensembles & trajectories Example using 18-crown-6 Quantum Mechanics (QM) Methods Schrödinger’s equation Semi-empirical (SE) Wave Functional Theory (WFT) Density Functional Theory (DFT) Hybrid QM/MM & MD Methods Comparison of hybrid methods 4 Useful for all system size ◦ Small molecules, proteins, material assemblies, surface science, etc … ◦ Based on Newtonian mechanics (classical mechanics) d F = (mv) dt ◦ The potential energy of the system is calculated using a force field € 5 An atom is considered as a single particle Example: H atom Particle variables: ◦ Radius (typically van der Waals radius) ◦ Polarizability ◦ Net charge Obtained from experiment or QM calculations ◦ Bond interactions Equilibrium bond lengths & angles from experiment or QM calculations 6 All atom approach ◦ Provides parameters for every atom in the system (including hydrogen) Ex: In –CH3 each atom is assigned a set of data MOLDEN MOLDEN (Radius, polarizability, netMOLDENMOLDENMOLDENMOLDENMOLDEN charge, -
Molecular Dynamics Study of the Stress–Strain Behavior of Carbon-Nanotube Reinforced Epon 862 Composites R
Materials Science and Engineering A 447 (2007) 51–57 Molecular dynamics study of the stress–strain behavior of carbon-nanotube reinforced Epon 862 composites R. Zhu a,E.Pana,∗, A.K. Roy b a Department of Civil Engineering, University of Akron, Akron, OH 44325, USA b Materials and Manufacturing Directorate, Air Force Research Laboratory, AFRL/MLBC, Wright-Patterson Air Force Base, OH 45433, USA Received 9 March 2006; received in revised form 2 August 2006; accepted 20 October 2006 Abstract Single-walled carbon nanotubes (CNTs) are used to reinforce epoxy Epon 862 matrix. Three periodic systems – a long CNT-reinforced Epon 862 composite, a short CNT-reinforced Epon 862 composite, and the Epon 862 matrix itself – are studied using the molecular dynamics. The stress–strain relations and the elastic Young’s moduli along the longitudinal direction (parallel to CNT) are simulated with the results being also compared to those from the rule-of-mixture. Our results show that, with increasing strain in the longitudinal direction, the Young’s modulus of CNT increases whilst that of the Epon 862 composite or matrix decreases. Furthermore, a long CNT can greatly improve the Young’s modulus of the Epon 862 composite (about 10 times stiffer), which is also consistent with the prediction based on the rule-of-mixture at low strain level. Even a short CNT can also enhance the Young’s modulus of the Epon 862 composite, with an increment of 20% being observed as compared to that of the Epon 862 matrix. © 2006 Elsevier B.V. All rights reserved. Keywords: Carbon nanotube; Epon 862; Nanocomposite; Molecular dynamics; Stress–strain curve 1. -
FORCE FIELDS for PROTEIN SIMULATIONS by JAY W. PONDER
FORCE FIELDS FOR PROTEIN SIMULATIONS By JAY W. PONDER* AND DAVIDA. CASEt *Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 51. Louis, Missouri 63110, and tDepartment of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037 I. Introduction. ...... .... ... .. ... .... .. .. ........ .. .... .... ........ ........ ..... .... 27 II. Protein Force Fields, 1980 to the Present.............................................. 30 A. The Am.ber Force Fields.............................................................. 30 B. The CHARMM Force Fields ..., ......... 35 C. The OPLS Force Fields............................................................... 38 D. Other Protein Force Fields ....... 39 E. Comparisons Am.ong Protein Force Fields ,... 41 III. Beyond Fixed Atomic Point-Charge Electrostatics.................................... 45 A. Limitations of Fixed Atomic Point-Charges ........ 46 B. Flexible Models for Static Charge Distributions.................................. 48 C. Including Environmental Effects via Polarization................................ 50 D. Consistent Treatment of Electrostatics............................................. 52 E. Current Status of Polarizable Force Fields........................................ 57 IV. Modeling the Solvent Environment .... 62 A. Explicit Water Models ....... 62 B. Continuum Solvent Models.......................................................... 64 C. Molecular Dynamics Simulations with the Generalized Born Model........ -
Force Fields for MD Simulations
Force Fields for MD simulations • Topology/parameter files • Where do the numbers an MD code uses come from? • How to make topology files for ligands, cofactors, special amino acids, … • How to obtain/develop missing parameters. • QM and QM/MM force fields/potential energy descriptions used for molecular simulations. The Potential Energy Function Ubond = oscillations about the equilibrium bond length Uangle = oscillations of 3 atoms about an equilibrium bond angle Udihedral = torsional rotation of 4 atoms about a central bond Unonbond = non-bonded energy terms (electrostatics and Lenard-Jones) Energy Terms Described in the CHARMm Force Field Bond Angle Dihedral Improper Classical Molecular Dynamics r(t +!t) = r(t) + v(t)!t v(t +!t) = v(t) + a(t)!t a(t) = F(t)/ m d F = ! U (r) dr Classical Molecular Dynamics 12 6 &, R ) , R ) # U (r) = . $* min,ij ' - 2* min,ij ' ! 1 qiq j ij * ' * ' U (r) = $ rij rij ! %+ ( + ( " 4!"0 rij Coulomb interaction van der Waals interaction Classical Molecular Dynamics Classical Molecular Dynamics Bond definitions, atom types, atom names, parameters, …. What is a Force Field? In molecular dynamics a molecule is described as a series of charged points (atoms) linked by springs (bonds). To describe the time evolution of bond lengths, bond angles and torsions, also the non-bonding van der Waals and elecrostatic interactions between atoms, one uses a force field. The force field is a collection of equations and associated constants designed to reproduce molecular geometry and selected properties of tested structures. Energy Functions Ubond = oscillations about the equilibrium bond length Uangle = oscillations of 3 atoms about an equilibrium bond angle Udihedral = torsional rotation of 4 atoms about a central bond Unonbond = non-bonded energy terms (electrostatics and Lenard-Jones) Parameter optimization of the CHARMM Force Field Based on the protocol established by Alexander D. -
Tinker-HP : Accelerating Molecular Dynamics Simulations of Large Complex Systems with Advanced Point Dipole Polarizable Force Fields Using Gpus and Multi-Gpus Systems
Tinker-HP : Accelerating Molecular Dynamics Simulations of Large Complex Systems with Advanced Point Dipole Polarizable Force Fields using GPUs and Multi-GPUs systems Olivier Adjoua,y Louis Lagardère*,y,z Luc-Henri Jolly,z Arnaud Durocher,{ Thibaut Very,x Isabelle Dupays,x Zhi Wang,k Théo Jaffrelot Inizan,y Frédéric Célerse,y,? Pengyu Ren,# Jay W. Ponder,k and Jean-Philip Piquemal∗,y,# ySorbonne Université, LCT, UMR 7616 CNRS, F-75005, Paris, France zSorbonne Université, IP2CT, FR2622 CNRS, F-75005, Paris, France {Eolen, 37-39 Rue Boissière, 75116 Paris, France xIDRIS, CNRS, Orsay, France kDepartment of Chemistry, Washington University in Saint Louis, USA ?Sorbonne Université, CNRS, IPCM, Paris, France. #Department of Biomedical Engineering, The University of Texas at Austin, USA E-mail: [email protected],[email protected] arXiv:2011.01207v4 [physics.comp-ph] 3 Mar 2021 Abstract We present the extension of the Tinker-HP package (Lagardère et al., Chem. Sci., 2018,9, 956-972) to the use of Graphics Processing Unit (GPU) cards to accelerate molecular dynamics simulations using polarizable many-body force fields. The new high-performance module allows for an efficient use of single- and multi-GPUs archi- 1 tectures ranging from research laboratories to modern supercomputer centers. After de- tailing an analysis of our general scalable strategy that relies on OpenACC and CUDA , we discuss the various capabilities of the package. Among them, the multi-precision possibilities of the code are discussed. If an efficient double precision implementation is provided to preserve the possibility of fast reference computations, we show that a lower precision arithmetic is preferred providing a similar accuracy for molecular dynamics while exhibiting superior performances. -
The Fip35 WW Domain Folds with Structural and Mechanistic Heterogeneity in Molecular Dynamics Simulations
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Biophysical Journal Volume 96 April 2009 L53–L55 L53 The Fip35 WW Domain Folds with Structural and Mechanistic Heterogeneity in Molecular Dynamics Simulations Daniel L. Ensign and Vijay S. Pande* Department of Chemistry, Stanford University, Stanford, California ABSTRACT We describe molecular dynamics simulations resulting in the folding the Fip35 Hpin1 WW domain. The simulations were run on a distributed set of graphics processors, which are capable of providing up to two orders of magnitude faster compu- tation than conventional processors. Using the Folding@home distributed computing system, we generated thousands of inde- pendent trajectories in an implicit solvent model, totaling over 2.73 ms of simulations. A small number of these trajectories folded; the folding proceeded along several distinct routes and the system folded into two distinct three-stranded b-sheet conformations, showing that the folding mechanism of this system is distinctly heterogeneous. Received for publication 8 September 2008 and in final form 22 January 2009. *Correspondence: [email protected] Because b-sheets are a ubiquitous protein structural motif, tories on the distributed computing environment, Folding@ understanding how they fold is imperative in solving the home (5). For these calculations, we utilized graphics pro- protein folding problem. Liu et al. (1) recently made a heroic cessing units (ATI Technologies; Sunnyvale, CA), deployed set of measurements of the folding kinetics of 35 three- by the Folding@home contributors. Using optimized code, stranded b-sheet sequences derived from the Hpin1 WW individual graphics processing units (GPUs) of the type domain. -
Multiscale Friction Simulation of Dry Polymer Contacts: Reaching Experimental Length Scales by Coupling Molecular Dynamics and Contact Mechanics
Multiscale Friction Simulation of Dry Polymer Contacts: Reaching Experimental Length Scales by Coupling Molecular Dynamics and Contact Mechanics Daniele Savio ( [email protected] ) Freudenberg Technology Innovation SE & Co. KG https://orcid.org/0000-0003-1908-2379 Jannik Hamann Fraunhofer Institute for Mechanics of Materials: Fraunhofer-Institut fur Werkstoffmechanik IWM Pedro A. Romero Freudenberg Technology Innovation SE & Co. KG Christoph Klingshirn Freudenberg FST GmbH Ravindrakumar Bactavatchalou Freudenberg Technology Innovation SE & Co. KG Martin Dienwiebel Fraunhofer Institute for Mechanics of Materials: Fraunhofer-Institut fur Werkstoffmechanik IWM Michael Moseler Fraunhofer Institute for Mechanics of Materials: Fraunhofer-Institut fur Werkstoffmechanik IWM Research Article Keywords: Coupling Molecular Dynamics, Contact Mechanics, Multiscale Friction Posted Date: February 23rd, 2021 DOI: https://doi.org/10.21203/rs.3.rs-223573/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Multiscale friction simulation of dry polymer contacts: reaching experimental length scales by coupling molecular dynamics and contact mechanics Daniele Savio1*, Jannik Hamann2, Pedro A. Romero1, Christoph Klingshirn3, Ravindrakumar Bactavatchalou1, Martin Dienwiebel2,4, Michael Moseler2,5 1 Freudenberg Technology Innovation SE & Co. KG, Weinheim, Germany 2 µTC Microtribology Center, Fraunhofer Institute for Mechanics of Materials IWM, Freiburg, Germany 3 Freudenberg FST GmbH, Weinheim, Germany 4 Karlsruhe Institute of Technology, Institute for Applied Materials, IAM-CMS, Karlsruhe, Germany 5 Institute of Physics, University of Freiburg, Freiburg, Germany *Corresponding author: [email protected] Abstract This work elucidates friction in Poly-Ether-Ether-Ketone (PEEK) sliding contacts through multiscale simulations. At the nanoscale, non-reactive classical molecular dynamics (MD) simulations of dry and water-lubricated amorphous PEEK-PEEK interfaces are performed. -
Computational Biophysics: Introduction
Computational Biophysics: Introduction Bert de Groot, Jochen Hub, Helmut Grubmüller Max Planck-Institut für biophysikalische Chemie Theoretische und Computergestützte Biophysik Am Fassberg 11 37077 Göttingen Tel.: 201-2308 / 2314 / 2301 / 2300 (Secr.) Email: [email protected] [email protected] [email protected] www.mpibpc.mpg.de/grubmueller/ Chloroplasten, Tylakoid-Membran From: X. Hu et al., PNAS 95 (1998) 5935 Primary steps in photosynthesis F-ATP Synthase 20 nm F1-ATP(synth)ase ATP hydrolysis drives rotation of γ subunit and attached actin filament F1-ATP(synth)ase NO INERTIA! Proteins are Molecular Nano-Machines ! Elementary steps: Conformational motions Overview: Computational Biophysics: Introduction L1/P1: Introduction, protein structure and function, molecular dynamics, approximations, numerical integration, argon L2/P2: Tertiary structure, force field contributions, efficient algorithms, electrostatics methods, protonation, periodic boundaries, solvent, ions, NVT/NPT ensembles, analysis L3/P3: Protein data bank, structure determination by NMR / x-ray; refinement L4/P4: Monte Carlo, normal mode analysis, principal components L5/P5: Bioinformatics: sequence alignment, Structure prediction, homology modelling L6/P6: Charge transfer & photosynthesis, electrostatics methods L7/P7: Aquaporin / ATPase: two examples from current research Overview: Computational Biophysics: Concepts & Methods L08/P08: MD Simulation & Markov Theory: Molecular Machines L09/P09: Free energy calculations: Molecular recognition L10/P10: Non-equilibrium thermodynamics: -
Introduction to Computational Chemistry: Molecular Dynamics
Introduction to Computational Chemistry: Molecular Dynamics Alexander B. Pacheco User Services Consultant LSU HPC & LONI [email protected] LSU HPC Training Series Louisiana State University April 27, 2011 High Performance Computing @ Louisiana State University - http://www.hpc.lsu.edu April 27, 2011 1/39 Outline 1 Tutorial Goals 2 Introduction 3 Molecular Dynamics 4 Fundamentals of Molecular Dynamics 5 Ab Initio Molecular Dynamics Theory 6 Computational Chemistry Programs 7 Example Jobs High Performance Computing @ Louisiana State University - http://www.hpc.lsu.edu April 27, 2011 2/39 Tutorial Goals Cover the fundamentals of Molecular Dynamics Simulation: Ab-Initio and Classical. Expose researchers to the theory and computational packages used for MD simulations. Worked out examples for various computational packages such as CPMD, Gaussian, GAMESS and NWCHEM. Linux machines, LONI and LSU HPC at /home/apacheco/CompChem. Go ahead with the examples if you want but hold off all questions until tutorial is complete. My Background: Ab-Initio Molecular Dynamics. Questions about examples/tutorials and/or using Electronic Structure codes for AIMD, email me at [email protected] or [email protected] High Performance Computing @ Louisiana State University - http://www.hpc.lsu.edu April 27, 2011 3/39 What is Computational Chemistry Computational Chemistry is a branch of chemistry that uses principles of computer science to assist in solving chemical problems. Uses the results of theoretical chemistry, incorporated into efficient computer programs. Application to single molecule, groups of molecules, liquids or solids. Calculates the structure and properties such as relative energies, charge distributions, dipole and multipole moments, spectroscopy, reactivity, etc.