Stable de novo protein design via joint conformational landscape and sequence optimization.

ABSTRACT: Generative protein modeling provides advanced tools for designing diverse protein sequences and structures. However, accurately modeling the conformational landscape and designing sequences remain critical challenges: ensuring that the designed sequence reliably folds into the target structure as its most stable conformation, and optimizing the sequence for a given suboptimal fixed input structure. In this study, we present a systematic analysis of jointly optimizing sequence-to-structure and structure-to-sequence mappings. This approach enables us to find optimal solutions for modeling the conformational landscape. We validate our approach with large-scale protein stability measurements, demonstrating that joint optimization is superior for designing stable proteins using a joint model (T

SUBMITTER: Cho Y 

PROVIDER: S-EPMC12764529 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature