Biomolecular Simulations under Realistic Macroscopic Salt Conditions

• DOI: 10.1021/acs.jpcb.7b11734
• Publication Date: 2018-04-13T06:09:51Z
• Authors: Gregory A. Ross; Ariën S. Rustenburg; Patrick B. Grinaway; Josh Fass; John D. Chodera
• Keywords: Ions; 0301 basic medicine; Tetrahydrofolate Dehydrogenase; 03 medical and health sciences; src-Family Kinases; Osmolar Concentration; Static Electricity; Water; Salts; Molecular Dynamics Simulation; DNA, B-Form; Monte Carlo Method

Biomolecular simulations are typically performed in an aqueous environment where the number of ions remains fixed for duration simulation, generally with either a minimally neutralizing ion or salt pairs intended to match macroscopic concentration. In contrast, real biomolecules experience local environments concentration is dynamic and may differ from bulk. The degree variability average deviation remains, as yet, unknown. Here, we describe theory implementation Monte Carlo osmostat that can be added explicit solvent molecular dynamics sample semigrand canonical ensemble which fluctuates dynamically during simulation. reproduces correct equilibrium statistics simulation volume exchange large reservoir at defined To achieve useful acceptance rates, method makes use nonequilibrium candidate (NCMC) moves monovalent water molecules alchemically transmuted using short trajectories, modified Metropolis-Hastings criterion ensuring ( Δμ, N, p, T) ∼1046× boost rates. We demonstrate how typical protein (DHFR tyrosine kinase Src) nucleic acid (Drew-Dickerson B-DNA dodecamer) systems exhibit distributions significantly fixed-salt bulk display fluctuations on same order magnitude average.