The second and subsequent waves of the coronavirus disease (COVID-19) have caused problems worldwide. Here, using objective analysis, we present the changes that occurred in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus has mutated in three major directions, resulting in three groups to date. The basic viral genome was identified in April and shared across all continents. However, the virus continued to mutate independently in each country after the closure of borders. Some variants with greater infectivity replaced the earlier ones and caused second waves of the disease. Some of them slowly entered other countries and caused epidemics. Going forward, these viruses could also serve as sources of further mutations.
Diffusion is a spontaneous process and one of the physicochemical phenomena responsible for molecular transport, the rate of which is governed mainly by the diffusion coefficient; however, few coefficients are available for small molecules. We have constructed a simple and convenient experimental system with agar-gel to measure the diffusion coefficients of sugars.
A theoretical method has also been developed to estimate diffusion coefficients by a combination of molecular modeling and the Stokes–Einstein equation, by which the coefficients of several sugars, amino acids, and drug molecules have been obtained. This time we have applied both experimental and theoretical approaches to estimate the diffusion coefficients of an additional 10 amino acids. The measured and calculated values are consistent with small deviations, i.e., the diffusion coefficients estimated by molecular modeling correspond well to the experimental data, which suggests that the potential use of the diffusion coefficient as an additional molecular property in drug screening has been enhanced.
We investigated electronic states of a complex of zinc metalloprotease ubiquitin ligase 2(UBR2) with its peptide ligand using ab initio fragment molecular orbital (FMO) calculations. UBR2 possesses three Zn ions and several residues of UBR2 are coordinated to each Zn ion to form an active site of UBR2. To provide a precise description of these coordination bonds, we included these residues in the same fragment as Zn ion in FMO calculations. The results revealed that all coordinated residues should be included in the same fragment as Zn ion for obtaining the converged results. This fact can be applicable equally to metalloproteases including other metal ions.
Article type: opinion
Subject area: The new results of the structural biology and related computational technologies of the structural biology
2022 Volume 22 Pages
Published: May 31, 2022
Released on J-STAGE: May 31, 2022
Structural biology comprises “Structured biology” based on folded structure and “Unstructured biology” based on unfolded structure. Principal of “Unstructured biology” is intrinsically disordered protein (IDP), in which the polypeptide chain is highly disordered under physiological conditions. The length of the disordered polypeptide may extend to several hundred residues or more. Further, in protein comprising multiple domains, long disordered polypeptides exist between domains, even if each domain has a regularly folded structure. Such polypeptide region is called intrinsically disordered region (IDR). Several IDPs and IDRs exist in living cells and play important biological roles in intracellular networks. Here, the biological significance of IDP and IDR from various viewpoints are described. Overall, this review aims to encourage further studies on “Unstructured biology” based on unfolded/disordered protein structure.