Showing papers by "Saraswathi Vishveshwara published in 2021"

Network Re-Wiring During Allostery and Protein-Protein Interactions: A Graph Spectral Approach

Abstract: The process of allostery is often guided by subtle changes in the non-covalent interactions between residues of a protein. These changes may be brought about by minor perturbations by natural processes like binding of a ligand or protein-protein interaction. The challenge lies in capturing minute changes at the residue interaction level and following their propagation at local as well as global distances. While macromolecular effects of the phenomenon of allostery are inferred from experiments, a computational microscope can elucidate atomistic-level details leading to such macromolecular effects. Network formalism has served as an attractive means to follow this path and has been pursued further for the past couple of decades. In this chapter some concepts and methods are summarized, and recent advances are discussed. Specifically, the changes in strength of interactions (edge weight) and their repercussion on the overall protein organization (residue clustering) are highlighted. In this review, we adopt a graph spectral method to probe these subtle changes in a quantitative manner. Further, the power of this method is demonstrated for capturing re-ordering of side-chain interactions in response to ligand binding, which culminates into formation of a protein-protein complex in β2-adrenergic receptors.

Insights into Mechanisms and Models for Studying Neurological Adverse Events Mediated by Pharmacokinetic Interactions between Clinical Drugs and Illicit Substances of Herbal and Fungal Origin

Abstract: Coadministration of herbs and fungi with clinical drugs can result in herb–drug and fungi–drug interactions, leading to adverse effects, including neurological and related adverse events. Many of the illicit substances are derived from herbs or fungi. Hence, adverse neurological events that arise from pharmacokinetics-based interactions of illicit substances of herbal/fungal origin with clinical drugs are of significant health burden. Despite the knowledge that concomitant usage of clinical drugs with illicit substances can often result in neurological and related adverse events, the underlying pharmacokinetics-based mechanisms of these interactions are poorly understood. This chapter briefly highlights the neurological and related adverse events associated with pharmacokinetics-based interactions between clinical drugs and commonly used illicit substances of herbal or fungal origin, such as ayahuasca, cannabis (marijuana), cocaine, psilocybin, khat, salvia, kratom, and mescaline. This chapter discusses a great deal of novel insights into the potential mechanisms of pharmacokinetics-based interactions between clinical drugs and illicit substances of herbal/fungal origin that may be responsible for neurological and related adverse events. Finally, this chapter provides insights into potential experimental models that can be used in studying these pharmacokinetic interactions that lead to neurological adverse events.