Biomolecules
Bone repair using BMP-2 is a promising therapeutic approach in clinical practices, however, high dosages required to be effective pose issues of cost and safety. The present study explores the potential of low dose BMP-2 treatment via…
With the advent of deep generative models in computational chemistry, in silico anticancer drug design has undergone an unprecedented transformation. While state-of-the-art deep learning approaches have shown potential in generating…
Homozygous mutations in the progranulin gene (GRN) are associated with neuronal ceroid lipofuscinosis 11 (CLN11), a rare lysosomal-storage disorder characterized by cerebellar ataxia, seizures, retinitis pigmentosa, and cognitive disorders,…
A variety of missense mutations and a stop mutation in the gene coding for transmembrane protein 240 (TMEM240) have been reported to be the causative mutations of spinocerebellar ataxia 21 (SCA21). We aimed to investigate the expression of…
Efficient molecular featurization is one of the major issues for machine learning models in drug design. Here we propose persistent Ricci curvature (PRC), in particular Ollivier persistent Ricci curvature (OPRC), for the molecular…
Generally, carbohydrate-active enzymes are studied using chromogenic substrates that provide quick and easy color-based detection of enzyme-mediated hydrolysis. In the case of feruloyl esterases, commercially available chromogenic ferulate…
The coding space of protein sequences is shaped by evolutionary constraints set by requirements of function and stability. We show that the coding space of a given protein family--the total number of sequences in that family--can be…
The antioxidant activity of baked foods is of utmost interest when envisioning enhancing their health benefits. Incorporating functional ingredients is challenging since their bioactivity naturally declines during baking. In this study, 3D…
Despite recent advancements in deep learning methods for protein structure prediction and representation, little focus has been directed at the simultaneous inclusion and prediction of protein backbone and sidechain structure information.…
Hydrostatic pressure is a common perturbation to probe the conformations of proteins. There are two common forms of pressure dependent potentials of mean force (PMFs) derived from hydrophobic molecules available for the coarse grained…
In the cell, proteins fold and perform complex functions through global structural rearrangements. Function requires a protein to be at the brink of stability to be susceptible to small environmental fluctuations, yet stable enough to…
Here, we show by solution nuclear magnetic resonance measurements that the urea-unfolded protein apoazurin becomes elongated when the synthetic crowding agent dextran 20 is present, in contrast to the prediction from the macromolecular…
Protein-ligand docking is an in silico tool used to screen potential drug compounds for their ability to bind to a given protein receptor within a drug-discovery campaign. Experimental drug screening is expensive and time consuming, and it…
Many pairwise additive force fields are in active use for intrinsically disordered proteins (IDPs) and regions (IDRs), some of which modify energetic terms to improve description of IDPs/IDRs, but are largely in disagreement with solution…
The amyloid state of proteins is widely studied with relevancy in neurology, biochemistry, and biotechnology. In contrast with amorphous aggregation, the amyloid state has a well-defined structure, consisting of parallel and anti-parallel…
Recently, there has been great interest in learning how to best represent proteins, specifically with fixed-length embeddings. Deep learning has become a popular tool for protein representation learning as a model's hidden layers produce…
Despite considerable progress, ab initio protein structure prediction remains suboptimal. A crowdsourcing approach is the online puzzle video game Foldit, that provided several useful results that matched or even outperformed…
The protein-protein interactions (PPIs) of 14-3-3 proteins are a model system for studying PPI stabilization. The complex natural product Fusicoccin A stabilizes many 14-3-3 PPIs but is not amenable for use in SAR studies, motivating the…
The pandemic prevalence of COVID-19 has become a very serious global health issue. Scientists all over the world have been heavily invested in the discovery of a drug to combat SARS-CoV-2. It has been found that RNA-dependent RNA Polymerase…
Antibiotic resistance is a worldwide challenge. A potential approach to block resistance is to simultaneously inhibit WT and known escape variants of the target bacterial protein. Here we applied an integrated computational and experimental…