Improved performance in CAPRI round 37 using LZerD docking and template‐based modeling with combined scoring functions

Abstract

We report our group's performance for protein-protein complex structure prediction and scoring in Round 37 of the Critical Assessment of PRediction of Interactions (CAPRI), an objective assessment of protein-protein complex modeling. We demonstrated noticeable improvement in both prediction and scoring compared to previous rounds of CAPRI, with our human predictor group near the top of the rankings and our server scorer group at the top. This is the first time in CAPRI that a server has been the top scorer group. To predict protein-protein complex structures, we used both multi-chain template-based modeling (TBM) and our protein-protein docking program, LZerD. LZerD represents protein surfaces using 3D Zernike descriptors (3DZD), which are based on a mathematical series expansion of a 3D function. Because 3DZD are a soft representation of the protein surface, LZerD is tolerant to small conformational changes, making it well suited to docking unbound and TBM structures. The key to our improved performance in CAPRI Round 37 was to combine multi-chain TBM and docking. As opposed to our previous strategy of performing docking for all target complexes, we used TBM when multi-chain templates were available and docking otherwise. We also describe the combination of multiple scoring functions used by our server scorer group, which achieved the top rank for the scorer phase.

SWISS-MODEL: homology modelling of protein structures and complexes

“…as constraints in the simulation of the docking process ( 13–15 ). Results from latest assessments show that significantly improved quality of models is obtained when multi-chain template information is available and used for modelling ( 16 ).…”

Predictive and Experimental Approaches for Elucidating Protein–Protein Interactions and Quaternary Structures

“…The LZerD [ 106 ] software suite provides both pairwise dockings with LZerD and asymmetric multimeric docking with Multi-LZerD. LZerD has demonstrated improved performance since its introduction to the CAPRI experiment due to its continued integration of template based modelling, docking and scoring functions [ 108 , 109 ]. Multimeric docking programs have limited themselves to symmetrical complexes, which makes Multi-LZerD particularly useful as it provides complex asymmetric predictions.…”

“…These are then combined using a genetic algorithm and several scoring methods are used, including clashing of atoms determined by atoms being with 3.0 Å of each other in each subunit. Furthermore, a physics-based scoring system that incorporates multiple scoring terms, where repulsive and attractive parts of the term are considered separately; an electrostatics term, which considers repulsive/attractive and short-range/long-range contributions individually; a hydrogen and disulphide bond term; two solvation terms; and a knowledge-based atom contact term [ 109 ].…”

AngularQA: Protein Model Quality Assessment with LSTM Networks

“…While the rate at which genomes can be sequenced has grown rapidly with the advent of automated systems, protein structures have still been limited to expensive, experimental observation through Nuclear Magnetic Resonance or X-ray crystallography (Jacobson and Sali 2004). While great progress has been made in computational prediction methods with the help of machine learning techniques Lai et al 2017;Peterson et al 2017;Shin, Christo er, and Kihara 2017;D. Li, Ju, and Zou 2016;Wei et al 2015;Dao et al 2018;C.-Q.…”