Conformational Entropy as a Potential Liability of Computationally Designed Antibodies.

ABSTRACT: In silico antibody discovery is emerging as a viable alternative to traditional in vivo and in vitro approaches. Many challenges, however, remain open to enabling the properties of designed antibodies to match those produced by the immune system. A major question concerns the structural features of computer-designed complementarity determining regions (CDRs), including the role of conformational entropy in determining the stability and binding affinity of the designed antibodies. To address this problem, we used enhanced-sampling molecular dynamics simulations to compare the free energy landscapes of single-domain antibodies (sdAbs) designed using structure-based (DesAb-HSA-D3) and sequence-based approaches (DesAbO), with that of a nanobody derived from llama immunization (Nb10). Our resul

SUBMITTER: Lohr T 

PROVIDER: S-EPMC9138470 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature