QwikMD — Integrative Molecular Dynamics Toolkit for Novices and Experts

The proper functioning of biomolecules in living cells requires them to assume particular structures and to undergo conformational changes. Both biomolecular structure and motion can be studied using a wide variety of techniques, but none offers the level of detail as do molecular dynamics (MD) simulations. Integrating two widely used modeling programs, namely NAMD and VMD, we have created a robust, user-friendly software, QwikMD, which enables novices and experts alike to address biomedically relevant questions, where often only molecular dynamics simulations can provide answers. Performing both simple and advanced MD simulations interactively, QwikMD automates as many steps as necessary for preparing, carrying out, and analyzing simulations while checking for common errors and enabling reproducibility. QwikMD meets also the needs of experts in the field, increasing the efficiency and quality of their work by carrying out tedious or repetitive tasks while enabling easy control of every step. Whether carrying out simulations within the live view mode on a small laptop or performing complex and large simulations on supercomputers or Cloud computers, QwikMD uses the same steps and user interface. QwikMD is freely available by download on group and personal computers. It is also available on the cloud at Amazon Web Services.

[1]  Gary J. Sullivan,et al.  Video Quality Evaluation Methodology and Verification Testing of HEVC Compression Performance , 2016, IEEE Transactions on Circuits and Systems for Video Technology.

[2]  Rafael C Bernardi,et al.  Hybrid QM/MM Molecular Dynamics Study of Benzocaine in a Membrane Environment: How Does a Quantum Mechanical Treatment of Both Anesthetic and Lipids Affect Their Interaction. , 2012, Journal of chemical theory and computation.

[3]  Viktor Hornak,et al.  HIV-1 protease flaps spontaneously open and reclose in molecular dynamics simulations. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Peter L. Freddolino,et al.  Molecular dynamics simulations of the complete satellite tobacco mosaic virus. , 2006, Structure.

[5]  T. Blundell,et al.  Comparative protein modelling by satisfaction of spatial restraints. , 1993, Journal of molecular biology.

[6]  Leonardo G. Trabuco,et al.  Molecular dynamics flexible fitting: a practical guide to combine cryo-electron microscopy and X-ray crystallography. , 2009, Methods.

[7]  Rafael C. Bernardi,et al.  Molecular dynamics simulations of large macromolecular complexes. , 2015, Current opinion in structural biology.

[8]  Klaus Schulten,et al.  Mechanism of substrate translocation by a ring-shaped ATPase motor at millisecond resolution. , 2015, Journal of the American Chemical Society.

[9]  Peter A. Kollman,et al.  AMBER: Assisted model building with energy refinement. A general program for modeling molecules and their interactions , 1981 .

[10]  Klaus Schulten,et al.  Rapid parameterization of small molecules using the force field toolkit , 2013, J. Comput. Chem..

[11]  Edward A Bayer,et al.  Applications of computational science for understanding enzymatic deconstruction of cellulose. , 2011, Current opinion in biotechnology.

[12]  Rafael C Bernardi,et al.  Cellulose degradation in the human gut: Ruminococcus champanellensis expands the cellulosome paradigm. , 2016, Environmental microbiology.

[13]  K. Schulten,et al.  Molecular dynamics study of unbinding of the avidin-biotin complex. , 1997, Biophysical journal.

[14]  T. Darden,et al.  Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems , 1993 .

[15]  Laxmikant V. Kale,et al.  NAMD2: Greater Scalability for Parallel Molecular Dynamics , 1999 .

[16]  Rafael C. Bernardi,et al.  Computational Methodologies for Real-Space Structural Refinement of Large Macromolecular Complexes. , 2016, Annual review of biophysics.

[17]  Carsten Kutzner,et al.  GROMACS 4:  Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. , 2008, Journal of chemical theory and computation.

[18]  Oliver Beckstein,et al.  MDAnalysis: A toolkit for the analysis of molecular dynamics simulations , 2011, J. Comput. Chem..

[19]  Jan H. Jensen,et al.  PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical pKa Predictions. , 2011, Journal of chemical theory and computation.

[20]  Klaus Gerwert,et al.  Ras and GTPase-activating protein (GAP) drive GTP into a precatalytic state as revealed by combining FTIR and biomolecular simulations , 2012, Proceedings of the National Academy of Sciences.

[21]  H. Berendsen,et al.  Molecular dynamics with coupling to an external bath , 1984 .

[22]  K. Schulten,et al.  Steered molecular dynamics and mechanical functions of proteins. , 2001, Current opinion in structural biology.

[23]  Klaus Schulten,et al.  A system for interactive molecular dynamics simulation , 2001, I3D '01.

[24]  Klaus Schulten,et al.  CryoEM and computer simulations reveal a novel kinase conformational switch in bacterial chemotaxis signaling , 2015, eLife.

[25]  H. Grubmüller,et al.  Energy barriers and driving forces in tRNA translocation through the ribosome , 2013, Nature Structural &Molecular Biology.

[26]  Berk Hess,et al.  GROMACS 3.0: a package for molecular simulation and trajectory analysis , 2001 .

[27]  Pedro G. Pascutti,et al.  The Structural Dynamics of the Flavivirus Fusion Peptide–Membrane Interaction , 2012, PloS one.

[28]  J. Mccammon,et al.  HIV‐1 protease molecular dynamics of a wild‐type and of the V82F/I84V mutant: Possible contributions to drug resistance and a potential new target site for drugs , 2004, Protein science : a publication of the Protein Society.

[29]  Rafael C. Bernardi,et al.  Enhanced sampling techniques in molecular dynamics simulations of biological systems. , 2015, Biochimica et biophysica acta.

[30]  Jianwu Wang,et al.  Progress towards Automated Kepler Scientific Workflows for Computer-aided Drug Discovery and Molecular Simulations , 2014, ICCS.

[31]  Steve Plimpton,et al.  Fast parallel algorithms for short-range molecular dynamics , 1993 .

[32]  Klaus Schulten,et al.  Atomic detail visualization of photosynthetic membranes with GPU-accelerated ray tracing , 2016, Parallel Comput..

[33]  Pedro G Pascutti,et al.  Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics , 2014, BMC Genomics.

[34]  Pedro G. Pascutti,et al.  Molecular dynamics study of biomembrane/local anesthetics interactions , 2009 .

[35]  Modesto Orozco,et al.  A theoretical view of protein dynamics. , 2014, Chemical Society reviews.

[36]  Klaus Schulten,et al.  Mapping Mechanical Force Propagation through Biomolecular Complexes. , 2015, Nano letters.

[37]  W. L. Jorgensen,et al.  Comparison of simple potential functions for simulating liquid water , 1983 .

[38]  Alexander D. MacKerell,et al.  Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone φ, ψ and side-chain χ(1) and χ(2) dihedral angles. , 2012, Journal of chemical theory and computation.

[39]  Jianpeng Ma,et al.  CHARMM: The biomolecular simulation program , 2009, J. Comput. Chem..

[40]  Adrian J Mulholland,et al.  Modelling enzyme reaction mechanisms, specificity and catalysis. , 2005, Drug discovery today.

[41]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[42]  James C. Phillips,et al.  Parallel Generalized Born Implicit Solvent Calculations with NAMD. , 2011, Journal of chemical theory and computation.

[43]  Qingguo Wang,et al.  MUFOLD: A new solution for protein 3D structure prediction , 2010, Proteins.

[44]  Gerrit Groenhof,et al.  GROMACS: Fast, flexible, and free , 2005, J. Comput. Chem..

[45]  Ling Tao,et al.  A highly efficient dilute alkali deacetylation and mechanical (disc) refining process for the conversion of renewable biomass to lower cost sugars , 2014, Biotechnology for Biofuels.

[46]  Ursula Rothlisberger,et al.  Polarization effects and charge transfer in the KcsA potassium channel. , 2006, Biophysical chemistry.

[47]  Peter M. Kasson,et al.  GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit , 2013, Bioinform..

[48]  Daniel R Roe,et al.  PTRAJ and CPPTRAJ: Software for Processing and Analysis of Molecular Dynamics Trajectory Data. , 2013, Journal of chemical theory and computation.

[49]  John E. Stone,et al.  Fast analysis of molecular dynamics trajectories with graphics processing units - Radial distribution function histogramming , 2011, J. Comput. Phys..

[50]  Klaus Schulten,et al.  Molecular dynamics study of enhanced Man5B enzymatic activity , 2014, Biotechnology for Biofuels.

[51]  Peter A. Kollman,et al.  AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules , 1995 .

[52]  Jens Meiler,et al.  ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules. , 2011, Methods in enzymology.

[53]  Laxmikant V. Kalé,et al.  Scalable molecular dynamics with NAMD , 2005, J. Comput. Chem..

[54]  V. Pande,et al.  Using massively parallel simulation and Markovian models to study protein folding: examining the dynamics of the villin headpiece. , 2006, The Journal of chemical physics.

[55]  Klaus Schulten,et al.  GPU-accelerated analysis and visualization of large structures solved by molecular dynamics flexible fitting. , 2014, Faraday discussions.

[56]  K Schulten,et al.  VMD: visual molecular dynamics. , 1996, Journal of molecular graphics.

[57]  Klaus Schulten,et al.  Ultrastable cellulosome-adhesion complex tightens under load , 2014, Nature Communications.

[58]  Klaus Schulten,et al.  GPU-accelerated molecular visualization on petascale supercomputing platforms , 2013, UltraVis@SC.

[59]  Matteo Ceccarelli,et al.  The Gating Mechanism of the Human Aquaporin 5 Revealed by Molecular Dynamics Simulations , 2013, PloS one.

[60]  M. Karplus,et al.  CHARMM: A program for macromolecular energy, minimization, and dynamics calculations , 1983 .

[61]  D. van der Spoel,et al.  GROMACS: A message-passing parallel molecular dynamics implementation , 1995 .

[62]  M. Karplus,et al.  Dynamics of folded proteins , 1977, Nature.

[63]  Klaus Schulten,et al.  Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics , 2013, Nature.

[64]  Alexander D. MacKerell,et al.  All-atom empirical potential for molecular modeling and dynamics studies of proteins. , 1998, The journal of physical chemistry. B.

[65]  Yang Zhang,et al.  I-TASSER: a unified platform for automated protein structure and function prediction , 2010, Nature Protocols.

[66]  Torsten Schwede,et al.  BIOINFORMATICS Bioinformatics Advance Access published November 12, 2005 The SWISS-MODEL Workspace: A web-based environment for protein structure homology modelling , 2022 .

[67]  Leonardo G. Trabuco,et al.  Flexible fitting of atomic structures into electron microscopy maps using molecular dynamics. , 2008, Structure.

[68]  D. Rickwood,et al.  Cell and Molecular Biology , 1998, The Journal of Steroid Biochemistry and Molecular Biology.

[69]  Taehoon Kim,et al.  CHARMM‐GUI: A web‐based graphical user interface for CHARMM , 2008, J. Comput. Chem..

[70]  J. Onuchic,et al.  Theory of protein folding: the energy landscape perspective. , 1997, Annual review of physical chemistry.

[71]  Holger Gohlke,et al.  The Amber biomolecular simulation programs , 2005, J. Comput. Chem..