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Updated: Jan 1, 2026

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins
Published on: July 8, 2025
Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction
Philip M Zakas1, Harrison C Brown1, Kristopher Knight2
1Program in Molecular and Systems Pharmacology, Laney Graduate School, Emory University, Atlanta, Georgia, USA.
Abstract:
Optimization of a protein's pharmaceutical properties is usually carried out by rational design and/or directed evolution. Here we test an alternative approach based on ancestral sequence reconstruction. Using available genomic sequence data on coagulation factor VIII and predictive models of molecular evolution, we engineer protein variants with improved activity, stability, and biosynthesis potential and reduced inhibition by anti-drug antibodies. In principle, this approach can be applied to any protein drug based on a conserved gene sequence.
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