Publications

The relationship between sequence variation and phenotype is poorly understood. Here, we use metabolomic analysis to elucidate the molecular mechanism underlying the filamentous phenotype of E. coli strains that carry destabilizing mutations in...

Every amino acid residue can influence a protein's overall stability, making stability highly susceptible to change throughout evolution. We consider the distribution of protein stabilities evolutionarily permittable under two previously reported protein...

Structure-based virtual screening is an important tool in early stage drug discovery that scores the interactions between a target protein and candidate ligands. As virtual libraries continue to grow (in excess of 10 molecules), so too do the resources...

Cotranslational folding depends on the folding speed and stability of the nascent protein. It remains difficult, however, to predict which proteins cotranslationally fold. Here, we simulate evolution of model proteins to investigate how native structure...

Directed evolution using random mutation in vast sequence space leads to the low probability of obtaining target proteins. Emerging engineering strategies with computational tools are developed for more trustable outcomes. We used some semi-rational...

Multivalent biopolymers phase separate into membrane-less organelles (MLOs) which exhibit liquid-like behavior. Here, we explore formation of prototypical MOs from multivalent proteins on various time and length scales and show that the kinetically...

The distribution of protein stability effects is known to be well approximated by a Gaussian distribution from previous empirical fits. Starting from first-principles statistical mechanics, we more rigorously motivate this empirical observation by...

Class A G-protein-coupled receptors (GPCRs) influence virtually every aspect of human physiology. Understanding receptor activation mechanism is critical for discovering novel therapeutics since about one-third of all marketed drugs target members of this...

The mechanisms of adaptation to inactivation of essential genes remain unknown. Here we inactivate dihydrofolate reductase (DHFR) by introducing D27G,N,F chromosomal mutations in a key catalytic residue with subsequent adaptation by an automated serial...

Cellobiose 2-epimerase (CE) is a promising industrial enzyme that can be utilized in the dairy industry. More thermostable CEs from different microorganisms are still needed for a higher lactulose productivity. This study demonstrated the feasibility to...

Human β2-microglobulin (b2m) protein is classically associated with dialysis-related amyloidosis (DRA). Recently, the single point mutant D76N was identified as the causative agent of a hereditary systemic amyloidosis affecting visceral organs. To get...

While reverse genetics and functional genomics have long affirmed the role of individual mutations in determining protein function, there have been fewer studies addressing how large-scale changes in protein sequences, such as in entire modular segments...