Mapping the space of protein binding sites with sequence-based protein language models.

Motivation: Binding sites are the key interfaces that determine a protein's biological activity, and therefore common targets for therapeutic intervention. Techniques that help us detect, compare, and contextualize binding sites are hence of immense interest to drug discovery.

Results: Here, we present an approach that integrates protein language models with a 3D tessellation technique to derive rich and versatile representations of binding sites that combine functional, structural, and evolutionary information with unprecedented detail.

DeepCDpred: Inter-residue distance and contact prediction for improved prediction of protein structure.

Rapid, accurate prediction of protein structure from amino acid sequence would accelerate fields as diverse as drug discovery, synthetic biology and disease diagnosis. Massively improved prediction of protein structures has been driven by improving the prediction of the amino acid residues that contact in their 3D structure. For an average globular protein, around 92% of all residue pairs are non-contacting, therefore accurate prediction of only a small percentage of inter-amino acid distances could increase the number of constraints to guide structure determination.

Protonation Kinetics Compromise Liposomal Fluorescence Assay of Membrane Permeation.

The membrane permeation of weak acids and bases couples to the ambient pH and can be studied using pH-sensitive dyes as reporters. Such fluorescence measurements with aliphatic amine drugs have revealed biexponential kinetics of permeation into liposomes (Eyer et al. J.

Lipid bilayer permeation of aliphatic amine and carboxylic acid drugs: rates of insertion, translocation and dissociation from MD simulations.

Aliphatic amines (AAs) and carboxylic acids (CAs) constitute the two most commonly occurring chemical groups among orally active drugs [Manallack, et al., ChemMedChem, 2013, 8, 242]. Here, we aim to rationalize this observation in terms of molecular properties that are essential for drug bioavailability.

Fabrication of 3D Controlled in vitro Microenvironments.

Microfluidics-based lab-on-a-chips have many advantages, one of which is to provide physiologically relevant settings for cell biology experiments. Thus there is an ever increasing interest in their fabrication. Our goal is to construct three dimensional (3D) Controlled in vitro Microenvironments (CivMs) that mimic the in vivo microenvironments.