CRAFT: a web-integrated cavity prediction tool based on flow transfer algorithm

Anuj Gahlawat; Anjali Singh; Hardeep Sandhu; Prabha Garg

doi:10.1186/s13321-024-00803-6

CRAFT: a web-integrated cavity prediction tool based on flow transfer algorithm

J Cheminform. 2024 Jan 30;16(1):12. doi: 10.1186/s13321-024-00803-6.

Authors

Anuj Gahlawat¹, Anjali Singh², Hardeep Sandhu¹, Prabha Garg³

Affiliations

¹ Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, 160062, Punjab, India.
² Department of Computer Science, Kurukshetra University, Kurukshetra, Haryana, India.
³ Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, 160062, Punjab, India. prabhagarg@niper.ac.in.

Abstract

Numerous computational methods, including evolutionary-based, energy-based, and geometrical-based methods, are utilized to identify cavities inside proteins. Cavity information aids protein function annotation, drug design, poly-pharmacology, and allosteric site investigation. This article introduces "flow transfer algorithm" for rapid and effective identification of diverse protein cavities through multidimensional cavity scan. Initially, it identifies delimiter and susceptible tetrahedra to establish boundary regions and provide seed tetrahedra. Seed tetrahedron faces are precisely scanned using the maximum circle radius to transfer seed flow to neighboring tetrahedra. Seed flow continues until terminated by boundaries or forbidden faces, where a face is forbidden if the estimated maximum circle radius is less or equal to the user-defined maximum circle radius. After a seed scanning, tetrahedra involved in the flow are clustered to locate the cavity. The CRAFT web interface integrates this algorithm for protein cavity identification with enhanced user control. It supports proteins with cofactors, hydrogens, and ligands and provides comprehensive features such as 3D visualization, cavity physicochemical properties, percentage contribution graphs, and highlighted residues for each cavity. CRAFT can be accessed through its web interface at http://pitools.niper.ac.in/CRAFT , complemented by the command version available at https://github.com/PGlab-NIPER/CRAFT/ .Scientific contribution: Flow transfer algorithm is a novel geometric approach for accurate and reliable prediction of diverse protein cavities. This algorithm employs a distinct concept involving maximum circle radius within the 3D Delaunay triangulation to address diverse van der Waals radii while existing methods overlook atom specific van der Waals radii or rely on complex weighted geometric techniques.

Keywords: CRAFT; Cavity prediction; Delaunay triangulation; Flow transfer algorithm; Geometrical methods; Maximum circle radius (MCR); Protein cavities.