We describe MUSCLE, a new computer program for creating multiple alignments of protein sequences. Elements of the algorithm include fast distance estimation using kmer counting, progressive alignment using a new profile function we call the logexpectation score, and refinement using treedependent restricted partitioning. The speed and accuracy of MUSCLE are compared with T-Coffee, MAFFT and CLUSTALW on four test sets of reference alignments: BAliBASE, SABmark, SMART and a new benchmark, PREFAB. MUSCLE achieves the highest, or joint highest, rank in accuracy on each of these sets. Without refinement, MUSCLE achieves average accuracy statistically indistinguishable from T-Coffee and MAFFT, and is the fastest of the tested methods for large numbers of sequences, aligning 5000 sequences of average length 350 in 7 min on a current desktop computer. The MUSCLE program, source code and PREFAB test data are freely available at http://www.drive5. com/muscle.

MUSCLE: multiple sequence alignment with high accuracy and high throughput

CHARMM (Chemistry at HARvard Macromolecular Mechanics) is a highly flexible computer program which uses empirical energy functions to model macromolecular systems. The program can read or model build structures, energy minimize them by first- or second-derivative techniques, perform a normal mode or molecular dynamics simulation, and analyze the structural, equilibrium, and dynamic properties determined in these calculations. The operations that CHARMM can perform are described, and some implementation details are given. A set of parameters for the empirical energy function and a sample run are included.

CHARMM: A program for macromolecular energy, minimization, and dynamics calculations

For a successful analysis of the relation between amino acid sequence and protein structure, an unambiguous and physically meaningful definition of secondary structure is essential. We have developed a set of simple and physically motivated criteria for secondary structure, programmed as a pattern-recognition process of hydrogen-bonded and geometrical features extracted from x-ray coordinates. Cooperative secondary structure is recognized as repeats of the elementary hydrogen-bonding patterns “turn” and “bridge.” Repeating turns are “helices,” repeating bridges are “ladders,” connected ladders are “sheets.” Geometric structure is defined in terms of the concepts torsion and curvature of differential geometry. Local chain “chirality” is the torsional handedness of four consecutive Cα positions and is positive for right-handed helices and negative for ideal twisted β-sheets. Curved pieces are defined as “bends.” Solvent “exposure” is given as the number of water molecules in possible contact with a residue. The end result is a compilation of the primary structure, including SS bonds, secondary structure, and solvent exposure of 62 different globular proteins. The presentation is in linear form: strip graphs for an overall view and strip tables for the details of each of 10.925 residues. The dictionary is also available in computer-readable form for protein structure prediction work.

Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features

6.2.2. Definition of Effective Properties 3064 6.3. Response Properties to Magnetic Fields 3066 6.3.1. Nuclear Shielding 3066 6.3.2. Indirect Spin−Spin Coupling 3067 6.3.3. EPR Parameters 3068 6.4. Properties of Chiral Systems 3069 6.4.1. Electronic Circular Dichroism (ECD) 3069 6.4.2. Optical Rotation (OR) 3069 6.4.3. VCD and VROA 3070 7. Continuum and Discrete Models 3071 7.1. Continuum Methods within MD and MC Simulations 3072

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Quantum mechanical continuum solvation models.

This article describes the software suite GROMACS (Groningen MAchine for Chemical Simulation) that was developed at the University of Groningen, The Netherlands, in the early 1990s. The software, written in ANSI C, originates from a parallel hardware project, and is well suited for parallelization on processor clusters. By careful optimization of neighbor searching and of inner loop performance, GROMACS is a very fast program for molecular dynamics simulation. It does not have a force field of its own, but is compatible with GROMOS, OPLS, AMBER, and ENCAD force fields. In addition, it can handle polarizable shell models and flexible constraints. The program is versatile, as force routines can be added by the user, tabulated functions can be specified, and analyses can be easily customized. Nonequilibrium dynamics and free energy determinations are incorporated. Interfaces with popular quantum-chemical packages (MOPAC, GAMES-UK, GAUSSIAN) are provided to perform mixed MM/QM simulations. The package includes about 100 utility and analysis programs. GROMACS is in the public domain and distributed (with source code and documentation) under the GNU General Public License. It is maintained by a group of developers from the Universities of Groningen, Uppsala, and Stockholm, and the Max Planck Institute for Polymer Research in Mainz. Its Web site is http://www.gromacs.org.

/pdf/gromacs-fast-flexible-and-free-15aazpel5u.pdf

GROMACS: Fast, flexible, and free

To determine whether the diabetic exchange lists or the glycemic index of foods better predicts postprandial responses to carbohydrate-containing foods eaten as part of a mixed meal, three test meals were developed and fed to 12 subjects with non-insulin-dependent diabetes mellitus (NIDDM) and 13 healthy subjects. Each test meal contained exactly the same exchanges (1 milk, 4 starch, 2 fruit, 2 meat, 3 fat, 1 vegetable). In one meal, foods of high glycemic index (GI) were used, in a second meal, foods of intermediate GI were used, and in a third meal foods of low GI were used. The total GIs of the meals were: high, 184; intermediate, 131; and low, 107, thus predicting responses to intermediate and low GI, which were 71 and 58%, respectively, of the responses to high GI. Although some of the observed differences in the glycemic responses to the test meals were statistically significant, primarily in healthy subjects, the differences were usually much 90% of the corresponding responses to high GI. In healthy subjects, only the plasma glucose area increment after the low-GI meal was close to the predicted response. High GI produced significantly greater insulin responses than low GI in healthy subjects. We conclude that the diabetic exchange lists more accurately predict postprandial responses to carbohydrate-containing foods eaten as part of a mixed meal than does the GI of foods. Moreover, our data suggest that the responses of healthy subjects to test meals do not accurately predict the responses of NIDDM subjects.

Comparison of Predictive Capabilities of Diabetic Exchange Lists and Glycemic Index of Foods

Evidence of turn and salt bridge contributions to β-hairpin stability: MD simulations of C-terminal fragment from the B1 domain of protein G

https://www.gastrojournal.org/article/0016-5085(95)90580-4/pdf

Paracellular intestinal transport of six-carbon sugars is negligible in the rat

Cryo-EM structure of a group II chaperonin in the prehydrolysis ATP-bound state leading to lid closure

We show that RNA base pairs have variable stability depending on their degree of solvation. This finding has far-reaching biological implications for nucleic acid structure in a partially solvated cellular environment such as inside RNA–protein complexes. Molecular dynamics simulations of partially solvated Watson–Crick RNA base pairs show that whereas water serves to destabilize a base pair by competing for and disrupting base–base hydrogen bonds, when sufficient water molecules are present, fewer hydrogen bonds are available to disrupt the base pairs and the destabilization effect is reduced. The result is that base pairs exist at a stability minimum when solvated in between 20 and 100 water molecules, the upper limit of which corresponds to the approximate number of water molecules contained in the first hydration shell.

https://www.pnas.org/content/pnas/104/30/12336.full.pdf

Michael Levitt

Papers

Comparison of Predictive Capabilities of Diabetic Exchange Lists and Glycemic Index of Foods

Evidence of turn and salt bridge contributions to β-hairpin stability: MD simulations of C-terminal fragment from the B1 domain of protein G

Paracellular intestinal transport of six-carbon sugars is negligible in the rat

Cryo-EM structure of a group II chaperonin in the prehydrolysis ATP-bound state leading to lid closure

Simulations of RNA base pairs in a nanodroplet reveal solvation-dependent stability