DOT2: Macromolecular docking with improved biophysical models

Abstract

Computational docking is a useful tool for predicting macromolecular complexes, which are often difficult to determine experimentally. Here we present the DOT2 software suite, an updated version of the DOT intermolecular docking program. DOT2 provides straightforward, automated construction of improved biophysical models based on molecular coordinates, offering checkpoints that guide the user to include critical features. DOT has been updated to run more quickly, allow flexibility in grid size and spacing, and generate a complete list of favorable candidate configu-rations. Output can be filtered by experimental data and rescored by the sum of electrostatic and atomic desolvation energies. We show that this rescoring method improves the ranking of correct complexes for a wide range of macromolecular interactions, and demonstrate that biologically relevant models are essential for biologically relevant results. The flexibility and versatility of DOT2 accommodate realistic models of complex biological systems, improving the likelihood of a successful docking outcome.

Binding Site Recognition and Docking Dynamics of a Single Electron Transport Protein: Cytochrome c2

“…The docking program DOT 2.0 28 was employed to construct models of the cyt. c 2 - bound bc 1 complex.…”

Improvements to the APBS biomolecular solvation software suite

“…Besides visualization and the processes described in "Preparing Biomolecular Structures," there are a number of other applications where APBS can be used. For example, during the past four years, the APBS-PDB2PQR software has been used in the postsimulation energetic analyses of molecular dynamics trajectories, 79 understanding protein-nanoparticle interactions, 80,81 understanding nucleic acid-ion interactions, 82 biomolecular docking 83 and ligand binding, 84 developing new coarse-grained protein models, 85 setting up membrane protein simulations, 86 and so on. APBS also plays a key role in PIPSA for protein surface electrostatics analysis 87 and BrownDye 88 and SDA 89 for simulation of protein-protein association kinetics through Brownian dynamics.…”

Overall energy conversion efficiency of a photosynthetic vesicle

“…This non-stationary behavior needs to be addressed by a coarser description like the ones employed for cell-scale modeling (Roberts et al, 2013).…”