Atomic-scale molecular dynamics and free energy calculations in explicit aqueous solvent are used to study the complex mechanism by which a molecule can intercalate between successive base pairs of DNA double helix. We have analyzed intercalation pathway for anticancer drug daunomycin using two different methods: metadynamics umbrella sampling. The resulting pathways found be consistent with one another point, within an equilibrium context, three-step process. Daunomycin initially binds...

The present communication examines how the dynamics of double helix affects Frenkel excitons that correspond to low-energy absorption band DNA. Two types oligomers, (dA)n.(dT)n and (dAdT)n/2.(dAdT)n/2, are studied theoretically, in framework exciton theory combination with quantum chemical calculations. properties states (energy, oscillator strength, degree delocalization, "anisotropy", etc.) found for canonical B-DNA geometries compared those obtained conformations extracted from molecular...

Considering the important role of cervical joint position sense on control human posture and locomotion, accurate reliable evaluation neck proprioceptive abilities appears great importance. Although cervicocephalic relocation test (CRT) to neutral head (NHP) usually is used for both research clinical purposes, its test-retest reliability has not been clearly established yet. The purpose present experiment was 1) evaluate CRT NHP 2) determine number trial recordings required ensure...

Purpose The purpose of this paper is to discuss overdose among those with criminal justice experience and recommend harm reduction strategies lessen risk vulnerable population. Design/methodology/approach Strategies are needed reduce deaths recent incarceration. Jails prisons at the epicenter opioid epidemic but a largely untapped setting for implementing education, assessment, medication assisted treatment, naloxone distribution programs. Federal, state, local plans commonly lack...

A combination of experiments and modeling reveals the influence alkyl chain lengths in biobased ZILs on biocompatibility towards various microorganisms.

Making the switch: The analysis of molecular dynamics simulations SRY-protein–DNA complex shows that, when SRY protein approaches correct DNA target sequence, it triggers a conformational switch and allows passage from nonspecifically bound to specifically state (see picture; dAXC=distance between protein). Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by...

DNA-Schalter: Eine Analyse von Moleküldynamik-Simulationen des Komplexes aus dem SRY-Protein und DNA zeigt, dass die Annäherung SRY-Proteins an richtige DNA-Sequenz einen Konformationsübergang der auslöst. Die löst Wechsel einem unspezifisch zu spezifisch gebundenen Zustand (siehe Bild; RMDS=Wurzel mittleren quadratischen Abweichung, dAXC=Abstand zwischen SRY-Protein).

Supervised injection facilities (SIFs) are legally sanctioned environments for people to inject drugs under medical supervision. SIFs currently operate in ten countries, but date, no SIF has been opened the USA. In light of increasing overdose mortality USA, this study evaluated willingness use a among youth who report non-medical prescription opioid (NMPO) use. Between January 2015 and February 2016, with recent NMPO were recruited participate Rhode Island Young Adult Prescription Drug...

Abstract The accurate description and analysis of protein–protein interfaces remains a challenging task. Traditional definitions, based on atomic contacts or changes in solvent accessibility, tend to over‐ underpredict the interface itself cannot discriminate active from less relevant parts. We here extend fast, parameter‐free purely geometric definition protein introduce shelling order Voronoi facets as novel measure for an atom's depth inside interface. Our 54 complexes reveals strong...

Highly specific transcriptional regulation depends on the cooperative association of transcription factors into enhanceosomes. Usually, their DNA-binding cooperativity originates from either direct interactions or DNA-mediated allostery. Here, we performed unbiased molecular simulations followed by protein-DNA unbinding and free energy profiling to study DNA recognition OCT4 SOX2, key components enhanceosomes in pluripotent cells. We found that SOX2 influences orientation dynamics DNA-bound...

The success of metaheuristic optimization methods has led to the development a large variety algorithm paradigms. However, no clearly dominates all its competitors on problems. Instead, underlying landscapes problems calls for algorithms solve them efficiently. It is thus prior importance have access mature and flexible software frameworks which allow an efficient exploration design space. Such should be enough accommodate any kind metaheuristics, open connect with higher-level optimization,...

The SRY gene on the Y chromosome is a necessary and sufficient condition for development of male phenotype involved in sex-reversal pathologies. associated protein also represents convenient model system study indirect protein−DNA recognition mechanisms, which local plasticity DNA may play more important role than direct interactions between bases. Using novel, low-bias restraint methodology, we have performed molecular dynamics simulations controlled dissociation from its cognate sequence....

This work proposes a simple yet accurate methodology to account for charge resonance in ionic clusters. The supersystem's model Hamiltonian is described via basis set of valence bond structures which the localized on given monomer, and whose intermolecular binding energies are computed using polarizable potential. coupling elements between these proportional an overlap integral relevant nonorthogonal monomer molecular orbitals. Ab initio calculations employed calibrate validate model, but...

The plasticity of membranes plays an important functional role in cells, cell components, and micelles, where bending, budding, remodeling implement numerous recognition communication processes. Comparatively, molecular simulation methods to induce, control, quantitatively characterize such deformations remain scarce. This work defines a novel collective coordinate associated with membrane which strives combine realism (by preserving the notion local atomic curvatures) low computational cost...

Non-medical prescription opioid (NMPO) use and depression frequently co-occur are mutually reinforcing in adults, yet NMPO younger populations has been under-studied. We examined the prevalence correlates of depressive symptomology among NMPO-using young adults. The Rhode Island Young Adult Prescription Drug Study (RAPiDS) recruited adults who reported past 30-day use. administered Center for Epidemiologic Studies Short Depression Scale (CES-D 10), used modified Poisson regression to...

We use a physics-based approach termed ADAPT to analyse the sequence-specific interactions of three proteins which bind DNA on side minor groove. The analysis is able estimate binding energy for all potential sequences, overcoming combinatorial problem via divide-and-conquer breaks protein–DNA interface down into series overlapping oligomeric fragments. All possible base sequences are studied each fragment. Energy minimisation with an all-atom representation and conventional force field...

Bacterial lectins are nonenzymatic sugar-binding proteins involved in the formation of biofilms and onset virulence. The weakness individual sugar–lectin interactions is compensated by potentially large number simultaneous copies such contacts, resulting high overall affinities marked specificities. Therapeutic compounds functionalized with sugar residues can compete host glycans for binding to only if they able take advantage this multivalent mechanism. Glycopeptide dendrimers, featuring...