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Biological small‐angle neutron scattering (SANS) instruments facilitate critical analysis of the structure and dynamics of complex biological systems. However, with the growth of experimental demands and the advances in optical systems design, a new neutron optical concept is necessary to overcome the limitations of current instruments. This work presents an approach to include experimental objectives (i.e. the science to be supported by a specific neutron scattering instrument) in the optimization of the neutron optical concept. The approach for a proposed SANS instrument at the Second Target Station of the Spallation Neutron Source at Oak Ridge National Laboratory, USA, is presented here. The instrument is simulated with the McStas software package. The optimization process is driven by an evolutionary algorithm using McStas output data, which are processed to calculate an objective function designed to quantify the expected performance of the simulated neutron optical configuration for the intended purpose. Each McStas simulation covers the complete instrument, from source to detector, including realistic sample scattering functions. This approach effectively navigates a high‐dimensional parameter space that is otherwise intractable; it allows the design of next‐generation SANS instruments to address specific scientific cases and has the potential to increase instrument performance compared with traditional design approaches. [ABSTRACT FROM AUTHOR]

Enzymes have evolved to rapidly and selectively hydrolyze diverse natural and anthropogenic polymers, but only a limited group of related enzymes have been shown to hydrolyze synthetic polyamides. In this work, we synthesized and characterized a panel of 95 diverse enzymes from the N-terminal nucleophile hydrolase superfamily with 30-50% pairwise amino acid identity. We found that nearly 40% of the enzymes had substantial nylon hydrolase activity, in many cases comparable to that of the best-characterized nylon hydrolase, NylC. There was no relationship between phylogeny and activity, nor any evidence of prior selection for nylon hydrolase activity. Several newly-identified hydrolases showed significant substrate selectivity, generating up to 20-fold higher product titers with Nylon 6,6 versus Nylon 6. Finally, we determined the crystal structure and oligomerization state of a Nylon 6,6-selective hydrolase to elucidate structural factors that could affect activity and selectivity. These new enzymes provide insights into the widespread potential for nylon hydrolase evolution and opportunities for analysis and engineering of improved hydrolases., Competing Interests: Conflict of Interest E.E.D, J.F.C, P.M.B.S-V, S.H.C, and J.K.M. are inventors on a patent application involving enzymes described in this work.

Abnormal peptide assembly and aggregation is associated with an array of neurodegenerative diseases including Alzheimer's disease (AD). A detailed understanding of how nanostructured materials such as oxidized graphene perturb the peptide assembly and subsequently induce fibril dissociation may open new directions for the development of potential AD treatments. Here, we investigate the impact of surface inhomogeneity of graphene oxide (GO) on the assembly of amyloid-beta Aβ 16-21 peptides on GO surfaces with different degrees of oxidation using molecular dynamics simulations. Interestingly, nonuniform GO nanosheets (in terms of oxidation sites) have a much stronger perturbation effect on the structure of Aβ 16-21 assembly. The Aβ peptides exhibit a remarkable tendency in binding to the scattered interfaces between unoxidized and oxidized regions, which induces the dissociation of Aβ amyloid fibril. These findings should deepen our understanding of surface-induced peptide dissociation and stimulate discovery of alternative AD treatments.

Unlike most matrix metalloproteinase (MMP) inhibitors, which target the conserved catalytic zinc site, Gd@C 82 (OH) 22 indirectly inhibits MMP-9 activity by binding at the ligand specificity S1' loop. The allosteric binding makes Gd@C 82 (OH) 22 a promising inhibitor selective for MMP-9. However, the hydrophobic nature of the aromatic carbon cage may cause Gd@C 82 (OH) 22 to self-aggregate in aqueous solutions, hence weakening the binding. In this study, we designed Gd@C 82 (OH) 22 derivatives aiming at improving the binding affinity for MMP-9. Upon a mutation that substitutes a new functional group (-PO 4 2- , -CH 2 CO 2 - , -CO 2 - , -NH 3 + , or -CONH 2 ) for a hydroxyl group on the fullerenol surface, we calculated the changes in the binding free energy to the catalytic domain of human MMP-9 using the free energy perturbation (FEP) method. We found that the higher the net charge of the functional group, the stronger the binding. Compared with Gd@C 82 (OH) 22 , Gd@C 82 (OH) 21 (PO 4 ) 2- binds at least 1.5 to 2.5 kcal mol -1 more strongly to MMP-9. The binding is specifically controlled by electrostatic interactions between the phosphate group and the charged residues at the binding site. In addition to the net charge, the binding free energy can be delicately adjusted by other factors, such as the functionalization site on Gd@C 82 (OH) 22 , the local environment of the putative binding site of MMP-9, and the presence of ions near the charged functional group. The results of our study shed light on the potential of developing Gd@C 82 (OH) 22 derivatives as nanodrugs for treating the pathological diseases associated with unregulated MMP-9 activity.