Advances in sequencing techniques and statistical methods have made it possible not only
to predict sequences of ancestral proteins but also to identify thousands of mutations in the …

The allosteric mechanism plays a key role in cellular functions of several PDZ domain
proteins (PDZs) and is directly linked to pharmaceutical applications; however, it is a …

β-lactamases are produced by many modern bacteria as a mechanism of resistance toward
β-lactam antibiotics, the most common antibiotics in use. β-lactamases, however, are ancient …

Using the perturbation-response scanning (PRS) technique, we study a set of 25 proteins
that display a variety of conformational motions upon ligand binding (eg, shear, hinge …

The canonical binding mode of PDZ domains to target motifs involves a small interface,
unlikely to fully account for PDZ-target interaction specificities. Here, we review recent work …

Globular PDZ domains typically serve as protein–protein interaction modules that regulate a
wide variety of cellular functions via recognition of short linear motifs (SLiMs). Often, PDZ …

Amino acid substitutions at nonconserved protein positions can have noncanonical and
“long-distance” outcomes on protein function. Such outcomes might arise from changes in …

As an important aspect of computer-aided drug design, structure-based drug design brought
a new horizon to pharmaceutical development. This in silico method permeates all aspects …

TEM-1 β-lactamase degrades β-lactam antibiotics with a strong preference for penicillins.
Sequence reconstruction studies indicate that it evolved from ancestral enzymes that …

Molecular dynamics (MD) simulation is a well-established method for understanding protein
dynamics. Conformations from unrestrained MD simulations have yet to be assessed for …