Calculation of accurate interatomic contact surface areas for the quantitative analysis of non-bonded molecular interactions

Abstract

Summary Intra- and intermolecular contact surfaces are routinely calculated for a large array of applications in bioinformatics but are typically approximated from differential solvent accessible surface area calculations and not calculated directly. These approximations do not properly take the effects of neighboring atoms into account and tend to deviate considerably from the true contact surface. We implemented an extension of the original Shrake-Rupley algorithm to accurately estimate interatomic contact surface areas of molecular structures and complexes. Our extended algorithm is able to calculate the contact area of an atom to all nearby atoms by directly calculating overlapping surface patches, taking into account the possible shielding effects of neighboring atoms. Here, we present a versatile software tool and web server for the calculation of contact surface areas, as well as buried surface areas and solvent accessible surface areas (SASA) for different types of biomolecules, such as proteins, nucleic acids and small organic molecules. Detailed results are provided in tab-separated values format for analysis and Protein Databank files for visualization. Direct contact surface area calculation resulted in improved accuracy in a benchmark with a non-redundant set of 245 protein–DNA complexes. SASA-based approximations underestimated protein–DNA contact surfaces on average by 40%. This software tool may be useful for surface-based intra- and intermolecular interaction analyses and scoring function development. Availability and implementation A web server, stand-alone binaries for Linux, MacOS and Windows and C++ source code are freely available from http://schuellerlab.org/dr_sasa/. Supplementary information Supplementary data are available at Bioinformatics online.

Cryo‐EM structure of native human uromodulin, a zona pellucida module polymer

“…Secondary structure was assigned using STRIDE (Frishman & Argos, 1995); Poisson–Boltzmann electrostatic calculations were performed using APBS/PDB2PQR (Jurrus et al , 2018); protein–protein interfaces were analyzed using PISA (Krissinel & Henrick, 2007), PIC (Tina et al , 2007) and the AnalyseComplex command of FoldX (Delgado et al , 2019); intermolecular contact surface areas were calculated with dr_sasa (Ribeiro et al , 2019). Structural figures and movies were generated with PyMOL (Schrödinger, LLC), UCSF Chimera (Pettersen et al , 2004)/ChimeraX (Goddard et al , 2018) and Illustrate (Goodsell et al , 2019); unless otherwise specified, they were based on the refined coordinates of UMOD fl .…”

A Quest for a Universal Plasma-Derived Antivenom Against All Elapid Neurotoxic Snake Venoms

“…The total accessible surface area of the 71 amino acid residue a-neurotoxin of N. siamensis, venom (PDB 1CTX; alphacobratoxin from Naja siamensis) is calculated to be about 5,206 sq. Å using a program described by Ribeiro et al (89).…”

Drug Discovery Targeting the Disorder-To-Order Transition Regions through the Conformational Diversity Mimicking and Statistical Analysis

“…Recent reverse docking study revealed that Autodock vina is biased (shows negative correlation) due to the contact surface area [ 28 ]. Therefore, we measured the protein–compound contact surface area [ 29 ] and normalized for the number of the molecular docking-involved atoms. We also evaluated the peptide model quality applying DOPE (discrete optimized protein energy) [ 30 ] because we obtained structures from the modeling web server.…”

“…Finally, we designed a new custom score for intrinsically disordered region direct targeting drug discovery evaluation, combining all the aforementioned scores. where is the smina (Autodock vina) score function [ 28 ], is the DOPE score function [ 30 ], and is protein–compound contact surface area calculation algorithm (dr_sasa) score [ 29 ]. Normalization of the dr_sasa score with the molecular docking-involved atom number ( n ) was empirical adjustment to calculate atomic contribution.…”