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Molecular dynamics simulations of biomolecular crystals at atomic resolution have the potential to recover information on dynamics and heterogeneity hidden in X-ray diffraction data. We present here 9.6 μs of dynamics in a small helical peptide crystal with 36 independent copies of the unit cell. The average simulation structure agrees with experiment to(More)
The parametrization and validation of the OPLS3 force field for small molecules and proteins are reported. Enhancements with respect to the previous version (OPLS2.1) include the addition of off-atom charge sites to represent halogen bonding and aryl nitrogen lone pairs as well as a complete refit of peptide dihedral parameters to better model the native(More)
We have identified a distal point mutation in streptavidin that causes a 1000-fold reduction in biotin binding affinity without disrupting the equilibrium complex structure. The F130L mutation creates a small cavity occupied by a water molecule; however, all neighboring side chain positions are preserved, and protein-biotin hydrogen bonds are unperturbed.(More)
We have developed the IPolQ method for fitting nonpolarizable point charges to implicitly represent the energy of polarization for systems in pure water. The method involves iterative cycles of molecular dynamics simulations to estimate the water charge density around the solute of interest, followed by quantum mechanical calculations at the MP2/cc-pV(T+d)Z(More)
The solvent reaction field potential of an uncharged protein immersed in simple point charge/extended explicit solvent was computed over a series of molecular dynamics trajectories, in total 1560 ns of simulation time. A finite, positive potential of 13-24 kbTec(-1) (where T=300 K), dependent on the geometry of the solvent-accessible surface, was observed(More)
We use classical molecular dynamics and 16 combinations of force fields and water models to simulate a protein crystal observed by room-temperature X-ray diffraction. The high resolution of the diffraction data (0.96 Å) and the simplicity of the crystallization solution (nearly pure water) make it possible to attribute any inconsistencies between the(More)
Hydration free energy calculations have become important tests of force fields. Alchemical free energy calculations based on molecular dynamics simulations provide a rigorous way to calculate these free energies for a particular force field, given sufficient sampling. Here, we report results of alchemical hydration free energy calculations for the set of(More)
We draw on an old technique for improving the accuracy of mesh-based field calculations to extend the popular Smooth Particle Mesh Ewald (SPME) algorithm as the Staggered Mesh Ewald (StME) algorithm. StME improves the accuracy of computed forces by up to 1.2 orders of magnitude and also reduces the drift in system momentum inherent in the SPME method by(More)
We have formulated the Energy by Linear Superposition of Corrections Approximation (ELSCA) for estimating the electrostatic and apolar solvation energy of bringing two proteins into close proximity or into contact as defined by the linearized Poisson-Boltzmann model and a linear function of the solvent-accessible surface area. ELSCA utilizes potentials of(More)
A 250 ns molecular dynamics simulation of the biotin-liganded streptavidin crystal lattice, including cryoprotectant molecules and crystallization salts, is compared to a 250 ns simulation of the lattice solvated with pure water. The simulation using detailed crystallization conditions preserves the initial X-ray structure better than the simulation using(More)