Abstract
Flexibility-rigidity index (FRI) has been developed as a robust, accurate, and efficient method for macromolecular thermal fluctuation analysis and B-factor prediction. The performance of FRI depends on its formulations of rigidity index and flexibility index. In this work, we introduce alternative rigidity and flexibility formulations. The structure of the classic Gaussian surface is utilized to construct a new type of rigidity index, which leads to a new class of rigidity densities with the classic Gaussian surface as a special case. Additionally, we introduce a new type of flexibility index based on the domain indicator property of normalized rigidity density. These generalized FRI (gFRI) methods have been extensively validated by the B-factor predictions of 364 proteins. Significantly outperforming the classic Gaussian network model, gFRI is a new generation of methodologies for accurate, robust, and efficient analysis of protein flexibility and fluctuation. Finally, gFRI based molecular surface generation and flexibility visualization are demonstrated.
Duc Nguyen
Associate Professor of Mathematics
Duc Nguyen develops mathematical and AI frameworks for molecular bioscience, drug discovery, and scientific computing. His group blends differential geometry, graph theory, and machine learning to build high-fidelity models for biomolecular systems, with notable wins in the D3R Grand Challenges and collaborations with Pfizer and Bristol Myers Squibb. Supported by multiple NSF awards, he has advised students and postdocs across theory and applications of AI-driven drug design.