Development of an algorithm to identify and characterize cavities in specific regions of three-dimensional structures of proteins.

Author(s)

Saulo Henrique Pires de Oliveira

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Matemática e Estatística (IME/SBI)
• Defense date: 2011-05-25

Examining board members

Paulo Sérgio Lopes de Oliveira; Artur Torres Cordeiro; Richard Charles Garratt

• Advisor: Paulo Sérgio Lopes de Oliveira

Abstract

The identification and characterization of geometrical and physical-chemical properties in protein vacant spaces aggregates important information for steering rational drug designing and functional characterization of binding and catalytic sites. Therefore, several softwares have been develop during the past two decades in order to perform such characterization. Nevertheless, the existing tools still present a series of limitations such as lack of precision, lack of integrability in large scale protocols, lack of customization capacity and the lack of a proper electrostatic depiction. We developed a new software, dubbed KV-Finder, in order to complement and extend the functionality of existing softwares, providing a systematic and more descriptive portrayal of protein vacant spaces. By employing a user-driven matrix modeling, our tool identifies and characterizes empty spaces in all sorts of protein topologies. The software quantifies the volume, the area and the shape of the surface, the residues that interact with the vacant spaces and a partial charge map of the computed surface. Our routine was integrated with a graphical molecular modeling software, providing the user with a simple and easy-to-use interface. KV-Finder has been validated with a distinct set of proteins and binding sites. The volume computation was carried in large scale, accompanying the evolution of the pocket volume in the ALDH superfamily. Compared with existing software, KV-Finder presents greater precision, greater accessibility and ease of integration in large scale protocols and visualization softwares. Also, the software possesses unique and innovative features such as the ability to segment and subsegment the empty spaces, a electrostatic depiction and a ligand interaction highlight feature. (AU)

• FAPESP's process: 09/06433-0 - Development of an algorithm to identify and characterize cavities in specific regions of three-dimensional structures of proteins.
• Grantee: Saulo Henrique Pires de Oliveira
• Support Opportunities: Scholarships in Brazil - Master