Antibody Engineering & Therapeutics 2025
Date & Time - December 14th-17th, 2025
Location - San Diego, California
Join us for a poster presentation by Sunidhi Lenka, Senior Scientist I at Schrödinger, titled “Improving antibody recycling and release through pH dependent engineering with FEP+ and cpHMD.” Stop by booth 419 to speak with Schrödinger scientists.
DEC 15 | 4:00PM Improving antibody recycling and release through pH dependent engineering with FEP+ and cpHMD
Speaker:
Sunidhi Lenka, Senior Scientist I, Schrödinger
Abstract:
pH-dependent binding is a valuable strategy in antibody engineering for improving antibody recycling, targeting acidic tumor microenvironments, and enabling controlled antigen release. Antibodies that bind tightly at neutral pH but dissociate under endosomal acidic conditions can be recycled to circulation while the antigen is directed to the lysosome for degradation. We developed a physics-based computational workflow that integrates FEP+ and constant-pH molecular dynamics to design and evaluate variants with tunable pH sensitivity. Using a representative antibody–antigen complex, histidine substitutions were predicted to modulate binding energetics across pH conditions. Experimental testing confirmed these predictions, showing strong binding at neutral pH and weaker binding at acidic pH. This approach provides a generalizable and efficient method for rationally designing pH-dependent antibodies with applications in Fc engineering and therapeutic antibody optimization.