Assessment of Two Restraint Potentials for Coarse-Grained Chemical-Cross-Link-Assisted Modeling of Protein Structures.

The influence of distance restraints from chemical cross-link mass spectroscopy (XL-MS) on the quality of protein structures modeled with the coarse-grained UNRES force field was assessed by using a protocol based on multiplexed replica exchange molecular dynamics, in which both simulated and experimental cross-link restraints were employed, for 23 small proteins. Six cross-links with upper distance boundaries from 4 Å to 12 Å (azido benzoic acid succinimide (ABAS), triazidotriazine (TATA), succinimidyldiazirine (SDA), disuccinimidyl adipate (DSA), disuccinimidyl glutarate (DSG), and disuccinimidyl suberate (BS)) and two types of restraining potentials ((i) simple flat-bottom Lorentz-like potentials dependent on side chain distance (all cross-links) and (ii) distance- and orientation-dependent potentials determined based on molecular dynamics simulations of model systems (DSA, DSG, BS, and SDA)) were considered. The Lorentz-like potentials with properly set parameters were found to produce a greater number of higher-quality models compared to unrestrained simulations than the MD-based potentials, because the latter can force too long distances between side chains.

Tautomeric equilibrium and spectroscopic properties of 8-azaguanine revealed by quantum chemistry methods.

8-azaguanine is a triazolopyrimidine nucleobase analog possessing potent antibacterial and antitumor activities, and it has been implicated as a lead molecule in cancer and malaria therapy. Its intrinsic fluorescence properties can be utilized for monitoring its interactions with biological polymers like proteins or nucleic acids. In order to better understand these interactions, it is important to know the tautomeric equilibrium of this compound.

Long-Time Dynamics of Selected Molecular-Motor Components Using a Physics-Based Coarse-Grained Approach.

Molecular motors are essential for the movement and transportation of macromolecules in living organisms. Among them, rotatory motors are particularly efficient. In this study, we investigated the long-term dynamics of the designed left-handed alpha/alpha toroid (PDB: 4YY2), the RBM2 flagellum protein ring from (PDB: 6SD5), and the V-type Na+-ATPase rotor in (PDB: 2BL2) using microcanonical and canonical molecular dynamics simulations with the coarse-grained UNRES force field, including a lipid-membrane model, on a millisecond laboratory time scale.

Why Purine Nucleoside Phosphorylase Ribosylates 2,6-Diamino-8-azapurine in Noncanonical Positions? A Molecular Modeling Study.

Protein nucleoside phosphorylase (PNP) is an enzyme that catalyzes a reversible conversion process (ribosylation and phosphorolysis) between nucleobases (purines) and their nucleosides. Experimental studies showed that calf PNP ribosylates purine analogues in specific positions: 2,6-diamino-8-azapurine in position 7 or 8 and 8-azaguanine in position 9 of the triazole ring. The reason for this phenomenon can be a result of different expositions of purine substrates to the channel leading to the binding site.

Metal Exchange in the Interprotein Zn -Binding Site of the Rad50 Hook Domain: Structural Insights into Cd -Induced DNA-Repair Inhibition.

Cd is a major genotoxic agent that readily displaces Zn in a multitude of zinc proteins, abrogates redox homeostasis, and deregulates cellular metalloproteome. To date, this displacement has been described mostly for cysteine(Cys)-rich intraprotein binding sites in certain zinc finger domains and metallothioneins. To visualize how a Zn -to-Cd swap can affect the target protein's status and thus understand the molecular basis of Cd -induced genotoxicity an intermolecular Zn -binding site from the crucial DNA repair protein Rad50 and its zinc hook domain were examined.