University of California, San Francisco
Emerging challenges for computer-aided drug design: macrocycles and allosteric modulators
Challenges in drug discovery, such as inhibiting protein-protein interfaces or increasing enzyme activity, have motivated my group to explore potential roles for computational chemistry beyond those addressed by docking, QSAR, and other widely used methods. I will discuss two of our efforts, to facilitate computer-aided design of (1) macrocycles, an emerging class of therapeutics intermediate between small-molecule and protein therapeutics; and (2) allosteric modulators, where the challenge is to optimize not just potency of binding but also achieve the desired modulation of function (activation or inhibition). Our computational approaches utilize all-atom simulations, guided by thermodynamic principles.