Unbiased molecular dynamics simulation

Molecular Dynamics (MD) simulation is a computer simulation technique used to monitor time- dependent processes of molecules where motion of each atom and molecule is computed by numerically solving Newton’s equations of motion.

Unbiased molecular dynamics simulation can be performed using the following software tools:

• Amber
• Amber Tools
• CHARMM
• Gromacs
• MOE
• NAMD

For examples of previously performed studies in which Unbiased molecular dynamics simulation was the primary method used, see the following example cases:

• Structural mechanism of a drug-binding process involving a large conformational change of the protein target.
• Long-time-step molecular dynamics can retard simulation of protein-ligand recognition process.
• Capturing Protein-Ligand Recognition Pathways in Coarse-Grained Simulation.
• Protein-ligand binding with the coarse-grained Martini model.
• Spontaneous Ligand Access Events to Membrane-Bound Cytochrome P450 2D6 Sampled at Atomic Resolution.
• How Effectively Can Adaptive Sampling Methods Capture Spontaneous Ligand Binding?
• Kinetics of Huperzine A Dissociation from Acetylcholinesterase via Multiple Unbinding Pathways.
• Binding Thermodynamics and Kinetics Calculations Using Chemical Host and Guest: A Comprehensive Picture of Molecular Recognition.

Unbiased molecular dynamics simulation was also used in the following examples:

• Predicting Ligand Binding Kinetics Using a Markovian Milestoning with Voronoi Tessellations Multiscale Approach.
• Transient States and Barriers from Molecular Simulations and the Milestoning Theory: Kinetics in Ligand-Protein Recognition and Compound Design.
• Ligand Binding Rate Constants in Heme Proteins Using Markov State Models and Molecular Dynamics Simulations.
• Can One Trust Kinetic and Thermodynamic Observables from Biased Metadynamics Simulations?: Detailed Quantitative Benchmarks on Millimolar Drug Fragment Dissociation.
• Quantitative Ranking of Ligand Binding Kinetics with a Multiscale Milestoning Simulation Approach.
• SEEKR: Simulation Enabled Estimation of Kinetic Rates, A Computational Tool to Estimate Molecular Kinetics and Its Application to Trypsin-Benzamidine Binding.
• Multiscale Simulation of Receptor-Drug Association Kinetics: Application to Neuraminidase Inhibitors.
• Bridging Microscopic and Macroscopic Mechanisms of p53-MDM2 Binding with Kinetic Network Models.
• Protein-peptide association kinetics beyond the seconds timescale from atomistic simulations.
• Protein conformational plasticity and complex ligand-binding kinetics explored by atomistic simulations and Markov models.
• Multiscale Estimation of Binding Kinetics Using Brownian Dynamics, Molecular Dynamics and Milestoning.
• On-the-Fly Learning and Sampling of Ligand Binding by High-Throughput Molecular Simulations.
• Complete reconstruction of an enzyme-inhibitor binding process by molecular dynamics simulations.