SWISH-X, an Expanded Approach to Detect Cryptic Pockets in Proteins and at Protein–Protein Interfaces

• DOI: 10.1021/acs.jctc.3c01318
• Publication Date: 2024-04-02T15:46:55Z
• Authors: Alberto Borsatto; Eleonora Gianquinto; Valerio Rizzi; Francesco Luigi G...
• Keywords: Surface protein

Protein-protein interactions mediate most molecular processes in the cell, offering a significant opportunity to expand set of known druggable targets. Unfortunately, targeting these can be challenging due their typically flat and featureless interaction surfaces, which often change as complex forms. Such surface changes may reveal hidden (cryptic) pockets. Here, we analyze well-characterized protein-protein harboring cryptic pockets investigate predictive power current computational methods. Based on our observations, developed new strategy, SWISH-X (SWISH Expanded), combines established pocket identification capabilities SWISH with rapid temperature range exploration OPES MultiThermal. is able reliably identify at interfaces while retaining its for revealing isolated proteins, such TEM-1 β-lactamase.