A5059988639- Protein Structure and Dynamics
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Human Pose and Action Recognition
- Human Motion and Animation
- Music and Audio Processing
- DNA and Nucleic Acid Chemistry
- Tactile and Sensory Interactions
- Autism Spectrum Disorder Research
- HIV/AIDS drug development and treatment
- Neuroscience and Music Perception
- Hand Gesture Recognition Systems
- HIV Research and Treatment
- Crystallization and Solubility Studies
- Spectroscopy and Quantum Chemical Studies
- Advanced NMR Techniques and Applications
- Emotion and Mood Recognition
- Music Technology and Sound Studies
- Bacteriophages and microbial interactions
- Mass Spectrometry Techniques and Applications
- Child Development and Digital Technology
- Calcium Carbonate Crystallization and Inhibition
- Action Observation and Synchronization
- Nanopore and Nanochannel Transport Studies
- Minerals Flotation and Separation Techniques
D. E. Shaw Research
2012-2022
University of Bologna
2022
University of Genoa
2013-2021
Larsen & Toubro (India)
2010
Curtin University
2005-2009
Scuola Internazionale Superiore di Studi Avanzati
2000-2009
RMIT University
2009
École Polytechnique Fédérale de Lausanne
2002-2005
Tecnologie Avanzate (Italy)
2004
ETH Zurich
2002
Recent advances in hardware and software have enabled increasingly long molecular dynamics (MD) simulations of biomolecules, exposing certain limitations the accuracy force fields used for such spurring efforts to refine these fields. modifications Amber CHARMM protein fields, example, improved backbone torsion potentials, remedying deficiencies earlier versions. Here, we further advance simulation by improving amino acid side-chain potentials ff99SB field. First, model alpha-helical systems...
An outstanding challenge in the field of molecular biology has been to understand process by which proteins fold into their characteristic three-dimensional structures. Here, we report results atomic-level dynamics simulations, over periods ranging between 100 μs and 1 ms, that reveal a set common principles underlying folding 12 structurally diverse proteins. In simulations conducted with single physics-based energy function, proteins, representing all three major structural classes,...
Molecular dynamics (MD) simulations are widely used to study protein motions at an atomic level of detail, but they have been limited time scales shorter than those many biologically critical conformational changes. We examined two fundamental processes in dynamics--protein folding and change within the folded state--by means extremely long all-atom MD conducted on a special-purpose machine. Equilibrium WW domain captured multiple unfolding events that consistently follow well-defined...
Molecular dynamics (MD) simulation is a valuable tool for characterizing the structural of folded proteins and should be similarly applicable to disordered with both regions. It has been unclear, however, whether any physical model (force field) used in MD simulations accurately describes proteins. Here, we select benchmark set 21 systems, including proteins, simulate these systems six state-of-the-art force fields, compare results over 9,000 available experimental data points. We find that...
Many proteins can be partially or completely disordered under physiological conditions. Structural characterization of these states using experimental methods challenging, since they are composed a structurally heterogeneous ensemble conformations rather than single dominant conformation. Molecular dynamics (MD) simulations should in principle provide an ideal tool for elucidating the composition and behavior at atomic level detail. Unfortunately, MD current physics-based models tend to...
Molecular dynamics simulations hold the promise of providing an atomic-level description protein folding that cannot easily be obtained from experiments. Here, we examine extent to which molecular mechanics force field used in such might influence observed pathways. To end, performed equilibrium a fast-folding variant villin headpiece using four different fields. In each simulation, large number transitions between unfolded and folded states, all cases, both rate structure native state were...
Molecular dynamics simulations provide a vehicle for capturing the structures, motions, and interactions of biological macromolecules in full atomic detail. The accuracy such simulations, however, is critically dependent on force field--the mathematical model used to approximate atomic-level forces acting simulated molecular system. Here we present systematic extensive evaluation eight different protein fields based comparisons experimental data with that reach previously inaccessible...
By suitably extending a recent approach [Bussi, G.; et al. J. Am. Chem. Soc. 2006, 128, 13435] we introduce powerful methodology that allows the parallel reconstruction of free energy system in virtually unlimited number variables. Multiple metadynamics simulations same at temperature are performed, biasing each replica with time-dependent potential constructed different set collective Exchanges between bias potentials variables periodically allowed according to exchange scheme. Due...
Anton is a recently completed special-purpose supercomputer designed for molecular dynamics (MD) simulations of biomolecular systems. The machine's specialized hardware dramatically increases the speed MD calculations, making possible first time simulation biological molecules at an atomic level detail periods on order millisecond---about two orders magnitude beyond previous state art. now running timescale which many critically important, but poorly understood phenomena are known to occur,...
Equilibrium molecular dynamics simulations, in which proteins spontaneously and repeatedly fold unfold, have recently been used to help elucidate the mechanistic principles that underlie folding of fast-folding proteins. The extent conclusions drawn from analysis such proteins, on microsecond timescale, apply millisecond or slower naturally occurring is, however, unclear. As a first attempt address this outstanding issue, we examine here ubiquitin, 76-residue-long protein found all...
Fully understanding the mechanisms of signaling proteins such as G protein-coupled receptors (GPCRs) will require characterization their conformational states and pathways connecting those states. The recent crystal structures beta(2)- beta(1)-adrenergic in a nominally inactive state constituted major advance toward this goal, but also raised new questions. Although earlier biochemical observations had suggested that these possessed set contacts between helices 3 6, known ionic lock, which...
Advances in simulation techniques and computing hardware have created a substantial overlap between the timescales accessible to atomic-level simulations those on which fastest-folding proteins fold. Here we demonstrate, using of four variants human villin headpiece, how spontaneous folding unfolding can provide direct access thermodynamic kinetic quantities such as rates, free energies, enthalpies, heat capacities, Φ-values, temperature-jump relaxation profiles. The quantitative comparison...
Autism spectrum conditions (autism) are diagnosed more frequently in boys than girls. Females with autism may have been under-identified due to not only a male-biased understanding of but also females' camouflaging. The study describes new technique that allows automated coding non-verbal mode communication (gestures) and offers the possibility objective, evaluation gestures, independent human judgment. EyesWeb software platform Kinect sensor during two demonstration activities ADOS-2...
Anton is a recently completed special-purpose supercomputer designed for molecular dynamics (MD) simulations of biomolecular systems. The machine's specialized hardware dramatically increases the speed MD calculations, making possible first time simulation biological molecules at an atomic level detail periods on order millisecond---about two orders magnitude beyond previous state art. now running timescale which many critically important, but poorly understood phenomena are known to occur,...
Trp-cage is a designed 20-residue polypeptide that, in spite of its size, shares several features with larger globular proteins.Although the system has been intensively investigated experimentally and theoretically, folding mechanism not yet fully understood. Indeed, some experiments suggest two-state behavior, while others point to presence intermediates. In this work we show that results bias-exchange metadynamics simulation can be used for constructing detailed thermodynamic kinetic model...
Significance The complex and often highly dynamic 3D structures of RNA molecules are central to their diverse cellular functions. Molecular dynamics (MD) simulations have played a major role in characterizing the structure proteins, but physical models (“force fields”) used for simulating nucleic acids substantially less accurate overall than those protein simulations, creating challenge MD studies RNA. Here, we report an force field capable describing structural thermodynamic properties...
Accurate computational prediction of protein structure represents a longstanding challenge in molecular biology and structure-based drug design. Although homology modeling techniques are widely used to produce low-resolution models, refining these models high resolution has proven difficult. With long enough simulations sufficiently accurate force fields, dynamics (MD) should principle allow such refinement, but efforts refine using MD have for the most part yielded disappointing results. It...
The accurate characterization of the structure and dynamics proteins in disordered states is a difficult problem at frontier structural biology whose solution promises to further our understanding protein folding intrinsically proteins. Molecular (MD) simulations have added considerably folded proteins, but accuracy with which force fields used such can describe unclear. In this work, using modern field, we performed 200 μs unrestrained MD simulation acid-unfolded state an experimentally...
The accuracy of atomistic physics-based force fields for the simulation biological macromolecules has typically been benchmarked experimentally using biophysical data from simple, often single-chain systems. In case proteins, careful refinement field parameters associated with torsion-angle potentials and use improved water models have enabled a great deal progress toward highly accurate such monomeric systems in both folded and, more recently, disordered states. living organisms, however,...
Chronic (persistent) pain (CP) affects 1 in 10 adults; clinical resources are insufficient, and anxiety about activity restricts lives. Technological aids monitor but lack necessary psychological support. This article proposes a new sonification framework, Go-with-the-Flow, informed by physiotherapists people with CP. The framework articulation of user-defined sonified exercise spaces (SESs) tailored to needs physical capabilities that enhance body movement awareness rebuild confidence...
Human ubiquitin has been extensively characterized using a variety of experimental and computational methods become an important model for studying protein dynamics. Nevertheless, it proven difficult to characterize the microsecond time scale dynamics this with atomistic resolution. Here we use unbiased computer simulation describe structural on picosecond millisecond scale. In simulation, interconverts between small number distinct states We find that conformations visited by free in...
Molecular dynamics (MD) simulations can describe protein motions in atomic detail, but transitions between conformational states sometimes take place on time scales that are infeasible or very expensive to reach by direct simulation. Enhanced sampling methods, the aim of which is increase efficiency MD simulations, have thus been extensively employed. The effectiveness such methods when applied complex biological systems like proteins, however, has difficult establish because even enhanced...
Intrinsically disordered proteins (IDPs), which in isolation do not adopt a well-defined tertiary structure but instead populate structurally heterogeneous ensemble of interconverting states, play important roles many biological pathways. IDPs often fold into ordered states upon binding to their physiological interaction partners (a so-called “folding-upon-binding” process), it has proven difficult obtain an atomic-level description the structural mechanisms by they so. Here, we describe...