Designer phospholipid capping ligands for soft metal halide nanocrystals.

The success of colloidal semiconductor nanocrystals (NCs) in science and optoelectronics is inextricable from their surfaces. The functionalization of lead halide perovskite NCs poses a formidable challenge because of their structural lability, unlike the well-established covalent ligand capping of conventional semiconductor NCs. We posited that the vast and facile molecular engineering of phospholipids as zwitterionic surfactants can deliver highly customized surface chemistries for metal halide NCs.

On the Mechanism of Alkylammonium Ligands Binding to the Surface of CsPbBr Nanocrystals.

CsPbBr nanocrystals (NCs) suffer from instabilities caused by the dynamic and labile nature of both the inorganic core and the organic-inorganic interface. Surface ligand engineering thus remains an imminent research topic. In this study, classical molecular dynamics simulations with an explicit solvent are used to gain insights into the inherent binding properties of three different alkylammonium ligands-primary dodecylammonium (DA), secondary didodecylammonium (DDA), and quaternary dimethyldi- dodecylammonium (DMDDA).

Electric field as a disaggregating agent for amyloid fibrils.

Folding and aggregation lie on competing reaction pathways in proteins. Altering the occupancy of one pathway is automatically relayed to the other pathway, leading to a shift in the balance between the two processes. In particular, it is known that the stabilization of the native state through mutations or solvent alterations is able to halt aggregation.

Effect of the Reaction Field on Molecular Forces and Torques Revealed by an Image-Charge Solvation Model.

We recently developed the Image-Charge Solvation Model (ICSM), which is an explicit/implicit hybrid model to accurately account for long-range electrostatic forces in molecular dynamics simulations [Lin et al., J. Chem.

Reduced atomic pair-interaction design (RAPID) model for simulations of proteins.

Increasingly, theoretical studies of proteins focus on large systems. This trend demands the development of computational models that are fast, to overcome the growing complexity, and accurate, to capture the physically relevant features. To address this demand, we introduce a protein model that uses all-atom architecture to ensure the highest level of chemical detail while employing effective pair potentials to represent the effect of solvent to achieve the maximum speed.

ICSM: An order N method for calculating electrostatic interactions added to TINKER.

We present an order N method for calculating electrostatic interactions that has been integrated into the molecular dynamics portion of the TINKER Molecular Modeling package. This method, introduced in a previous paper [J. Chem.

The mechanism of the converter domain rotation in the recovery stroke of myosin motor protein.

Upon ATP binding, myosin motor protein is found in two alternative conformations, prerecovery state M* and postrecovery state M**. The transition from one state to the other, known as the recovery stroke, plays a key role in the myosin functional cycle. Despite much recent research, the microscopic details of this transition remain elusive.

Interactions between relay helix and Src homology 1 (SH1) domain helix drive the converter domain rotation during the recovery stroke of myosin II.

Myosin motor protein exists in two alternative conformations, prerecovery state M* and postrecovery state M**, on adenosine triphosphate binding. The details of the M*-to-M** transition, known as the recovery stroke to reflect its role as the functional opposite of the force-generating power stroke, remain elusive. The defining feature of the postrecovery state is a kink in the relay helix, a key part of the protein involved in force generation.

Early stages of the recovery stroke in myosin II studied by molecular dynamics simulations.

The recovery stroke is a key step in the functional cycle of muscle motor protein myosin, during which pre-recovery conformation of the protein is changed into the active post-recovery conformation, ready to exersice force. We study the microscopic details of this transition using molecular dynamics simulations of atomistic models in implicit and explicit solvent. In more than 2 μs of aggregate simulation time, we uncover evidence that the recovery stroke is a two-step process consisting of two stages separated by a time delay.

Effect of atom- and group-based truncations on biomolecules simulated with reaction-field electrostatics.

The performance of the reaction-field method of electrostatics is tested in molecular dynamics simulations of protein human interleukin-4 and a short DNA fragment in explicit solvent. Two truncation schemes are considered: one based on the position of atomic charges in water molecules and the other on the position of groups of charges. The group-based truncation leads to the melting of the DNA double helix.

Ionic solvation studied by image-charge reaction field method.

In a preceding paper [J. Chem. Phys.

An image-based reaction field method for electrostatic interactions in molecular dynamics simulations of aqueous solutions.

In this paper, a new solvation model is proposed for simulations of biomolecules in aqueous solutions that combines the strengths of explicit and implicit solvent representations. Solute molecules are placed in a spherical cavity filled with explicit water, thus providing microscopic detail where it is most needed. Solvent outside of the cavity is modeled as a dielectric continuum whose effect on the solute is treated through the reaction field corrections.

A new FFT-based algorithm to compute Born radii in the generalized Born theory of biomolecule solvation.

In this paper, a new method for calculating effective atomic radii within the generalized Born (GB) model of implicit solvation is proposed, for use in computer simulations of bio-molecules. First, a new formulation for the GB radii is developed, in which smooth kernels are used to eliminate the divergence in volume integrals intrinsic in the model. Next, the Fast Fourier Transform (FFT) algorithm is applied to integrate smoothed functions, taking advantage of the rapid spectral decay provided by the smoothing.

Microscopic factors that control beta-sheet registry in amyloid fibrils formed by fragment 11-25 of amyloid beta peptide: insights from computer simulations.

Short fragments of amyloidogenic proteins are widely used as model systems in studies of amyloid formation. Fragment 11-25 of the amyloid beta protein involved in Alzheimer's disease (Abeta11-25) was recently shown to form amyloid fibrils composed of anti-parallel beta-sheets. Interestingly, fibrils grown under neutral and acidic conditions were seen to possess different registries of their inter-beta-strand hydrogen bonds.

Amyloid beta-protein: experiment and theory on the 21-30 fragment.

The structure of the 21-30 fragment of the amyloid beta-protein (Abeta) was investigated by ion mobility mass spectrometry and replica exchange dynamics simulations. Mutations associated with familial Alzheimer's disease (E22G, E22Q, E22K, and D23N) of Abeta(21-30) were also studied, in order to understand any structural changes that might occur with these substitutions. The structure of the WT peptide shows a bend and a perpendicular turn in the backbone which is maintained by a network of D23 hydrogen bonding.

Removing systematic errors in interionic potentials of mean force computed in molecular simulations using reaction-field-based electrostatics.

The performance of reaction-field methods to treat electrostatic interactions is tested in simulations of ions solvated in water. The potential of mean force between sodium chloride pair of ions and between side chains of lysine and aspartate are computed using umbrella sampling and molecular dynamics simulations. It is found that in comparison with lattice sum calculations, the charge-group-based approaches to reaction-field treatments produce a large error in the association energy of the ions that exhibits strong systematic dependence on the size of the simulation box.

Effects of familial Alzheimer's disease mutations on the folding nucleation of the amyloid beta-protein.

The effect of single amino acid substitutions associated with the Italian (E22K), Arctic (E22G), Dutch (E22Q) and Iowa (D23N) familial forms of Alzheimer's disease and cerebral amyloid angiopathy on the structure of the 21-30 fragment of the Alzheimer amyloid beta-protein (Abeta) is investigated by replica-exchange molecular dynamics simulations. The 21-30 segment has been shown in our earlier work to adopt a bend structure in solution that may serve as the folding nucleation site for Abeta. Our simulations reveal that the 24-28 bend motif is retained in all E22 mutants, suggesting that mutations involving residue E22 may not affect the structure of the folding nucleation site of Abeta.

Role of the familial Dutch mutation E22Q in the folding and aggregation of the 15-28 fragment of the Alzheimer amyloid-beta protein.

Amyloid fibrils, large ordered aggregates of amyloid beta proteins (Abeta), are clinical hallmarks of Alzheimer's disease (AD). The aggregation properties of amyloid beta proteins can be strongly affected by single-point mutations at positions 22 and 23. The Dutch mutation involves a substitution at position 22 (E22Q) and leads to increased deposition rates of the AbetaE22Q peptide onto preseeded fibrils.

Stability of a protein tethered to a surface.

Surface-tethered proteins are increasingly being used in a variety of experimental situations, and they are the basis for many new technologies. Nevertheless, a thorough understanding of how a surface can impact the native state stability of an attached protein is lacking. In this work, the authors use molecular dynamics simulations of a model beta-barrel protein to investigate how surface tethering influences native state stability.

The structure of the Alzheimer amyloid beta 10-35 peptide probed through replica-exchange molecular dynamics simulations in explicit solvent.

The conformational states sampled by the Alzheimer amyloid beta (10-35) (Abeta 10-35) peptide were probed using replica-exchange molecular dynamics (REMD) simulations in explicit solvent. The Abeta 10-35 peptide is a fragment of the full-length Abeta 40/42 peptide that possesses many of the amyloidogenic properties of its full-length counterpart. Under physiological temperature and pressure, our simulations reveal that the Abeta 10-35 peptide does not possess a single unique folded state.

Elucidating amyloid beta-protein folding and assembly: A multidisciplinary approach.

Oligomeric, neurotoxic amyloid protein assemblies are thought to be causative agents in Alzheimer's and other neurodegenerative diseases. Development of oligomer-specific therapeutic agents requires a mechanistic understanding of the oligomerization process. This is a daunting task because amyloidogenic protein oligomers often are metastable and comprise structurally heterogeneous populations in equilibrium with monomers and fibrils.

Folding landscapes of the Alzheimer amyloid-beta(12-28) peptide.

The energy landscape for folding of the 12-28 fragment of the Alzheimer amyloid beta (Abeta) peptide is characterized using replica-exchange molecular dynamics simulations with an all-atom peptide model and explicit solvent. At physiological temperatures, the peptide exists mostly as a collapsed random coil, populating a small fraction (less than 10%) of hairpins with a beta-turn at position V18F19, with another 10% of hairpin-like conformations possessing a bend rather than a turn in the central VFFA positions. A small fraction of the populated states, approximately 14%, adopt polyproline II (PPII) conformations.

The influence of different treatments of electrostatic interactions on the thermodynamics of folding of peptides.

Replica exchange molecular dynamics simulations were performed to investigate the effects of different electrostatic treatments on the structure and thermodynamics of a small beta-hairpin forming peptide. Three different electrostatic schemes were considered: regular cutoffs, generalized reaction field (GRF), and particle mesh Ewald (PME), with the peptide modeled using OPLS/AA all-atom force field with explicit TIP3P water. Both the GRF and PME methods yielded results consistent with experiment, with free energy surfaces displaying a single minimum corresponding to the native beta-hairpin structure.

Structure of the 21-30 fragment of amyloid beta-protein.

Folding and self-assembly of the 42-residue amyloid beta-protein (Abeta) are linked to Alzheimer's disease (AD). The 21-30 region of Abeta, Abeta(21-30), is resistant to proteolysis and is believed to nucleate the folding of full-length Abeta. The conformational space accessible to the Abeta(21-30) peptide is investigated by using replica exchange molecular dynamics simulations in explicit solvent.

Effects of surface tethering on protein folding mechanisms.

The folding mechanisms of proteins are increasingly being probed through single-molecule experiments in which the protein is immobilized on a surface. Nevertheless, a clear understanding of how the surface might affect folding, and whether or not it changes folding from its bulk behavior, is lacking. In this work, we use molecular dynamics simulations of a model beta-barrel protein tethered to a surface to systematically investigate how the surface impacts folding.