蛋白质结构预测16 Scoring Functions for De Novo Protein

Scoring Functions for De Novo Protein Structure Prediction Revisited Shing-Chung Ngan, Ling-Hong Hung, Tianyun Liu, and Ram Samudrala Summary De novo protein structure prediction methods attempt to predict tertiary structures from sequences based on general principles that govern protein folding energetics and/or statistical tendencies of conformational features that native structures acquire, without the use of explicit templates. A general paradigm for de novo prediction involves sampling the conformational space, guided by scoring functions and other sequence-dependent biases, such that a large set of candidate (“decoy”) structures are generated, and then selecting native-like conformations from those decoys using scoring functions as well as conformer clustering. High-resolution refinement is sometimes used as a final step to fine-tune native-like structures. There are two major classes of scoring functions. Physics-based functions are based on mathematical models describing aspects of the known physics of molecular interaction. Knowledge-based functions are formed with statistical models capturing aspects of the properties of native protein conformations. We discuss the implementation and use of some of the scoring functions from these two classes for de novo structure prediction in this chapter. Key Words: De novo; physics-based; knowledge-based; potential; protein folding. 1. Introduction The success of large-scale genome sequencing efforts has spurred structural genomic initiatives, with the goal of determining as many protein folds as possible (1–4). At present, structural determination by crystallography and nuclear magnetic resonance (NMR) techniques are still slow and expensive in terms of manpower and resources, despite attempts to automate the From: Methods in Molecular Biology, vol. 413: Protein Structure Prediction, Second Edition Edited by: M. Zaki and C. Bystroff ? Humana Press Inc., Totowa, NJ 243244 Ngan et al. processes. Computational structure