Carlos Alemán

Self-Assembly of a Designed Amyloid Peptide Containing the Functional Thienylalanine Unit

The self-assembly of a peptide based on a sequence from the amyloid beta peptide but incorporating the non-natural amino acid beta-2-thienylalanine (2-Thi) has been investigated in aqueous and methanol solutions. The peptide AAKLVFF was used as a design motif, replacing the phenylalanine residues (F) with 2-Thi units to yield (2-Thi)(2-Thi)VLKAA. The 2-Thi residues are expected to confer interesting electronic properties due to charge delocalization and pi-stacking. The peptide is shown to form beta-sheet-rich amyloid fibrils with a twisted morphology, in both water and methanol solutions at sufficiently high concentration. The formation of a self-assembling hydrogel is observed at high concentration. Detailed molecular modeling using molecular dynamics methods was performed using NOE constraints provided by 2D-NMR experiments. The conformational and charge properties of 2-Thi were modeled using quantum mechanical methods, and found to be similar to those previously reported for the beta-3-thienylalanine analogue. The molecular dynamics simulations reveal well-defined folded structures (turn-like) in dilute aqueous solution, driven by self-assembly of the hydrophobic aromatic units, with charged lysine groups exposed to water.

A new scaling procedure to correct semiempirical MEP and MEP-derived properties

SummaryThe MNDO, AM1, PM3, and ab initio 6–31G* and 6–31+G* MEPs for 21 neutral and 12 charged molecules were computed in layers ranging from 1.2 to 2.0 times the van der Waals radii of atoms. Semiempirical and ab initio MEPs for each layer and two groups of layers were compared to gain insight into the relationships between semiempirical and ab initio MEPs. A detailed statistical study allowed us to obtain a new set of scaling coefficients able to correct the semiempirical MEPs to provide better representations of the ab initio values. The corrected semiempirical MEPs were used to obtain electrostatic charges, whose quality was tested by the comparison between semiempirical Coulombic MEPs and ab initio quantum mechanical MEPs.

On the suitability of semiempirical calculations as sources of force field parameters

SummaryThe suitability of Dewars Hamiltonians as a source of bonded force field parameters is explored from the comparison analysis between up to 270 semiempirically derived force field parameters and experimentally derived values reported in some of the most popular force fields. From the statistical analysis of the results, some general conclusions about the semiempirical parametrization are formulated.

Performance of SuSi: A method for generating atomistic models of amorphous polymers based on a random search of energy minima

The performance of a recently developed method to generate representative atomistic models of amorphous polymers has been investigated. This method, which is denoted SuSi, can be defined as a random generator of energy minima. The effects produced by different parameters used to define the size of the system and the characteristics of the generation algorithm have been examined. Calculations have been performed on poly(L,D‐lactic) acid (ρ = 1.25 g/cm3) and nylon 6 (ρ = 1.084 g/cm3), which are important commercial polymers.

MCDP: an advanced tool to simulate comb-like polymers

A strategy to study polymeric systems with ordered structures, and in particular comb‐like polymers, is presented. These are dense systems for which atomistic simulations with conventional methods are difficult or even impracticable. The strategy, which has been incorporated into a computer program named MCDP, is based on a Configuration Bias Monte Carlo algorithm and a method to investigate the structure of crystalline polymers using force‐field calculations. To obtain a maximum efficiency, the MCDP computer program has been optimized and parallelized. The ability of MCDP to investigate ordered polymers have been tested by simulating two complex systems: (1) the crystal structure of poly(4‐methyl‐1‐pentene), and (2) the biphasic structure of poly(α‐octyl‐β‐L‐aspartate), a comb‐like polyamide derived from β‐amino acids. The results obtained from MCDP simulations demonstrates the efficiency and reliability of this method to study both the NVT and NPT behavior of ordered dense polymers.

Monte Carlo structural investigation of helical poly(β-l-aspartate)s containing linear alkyl side chains

Abstract Three representative members of the family of poly(α-alkyl β- l -aspartate)s (PAALA-12, -16 and -18) have been investigated using Monte Carlo simulation of an atomistically explicit model. At the temperatures investigated, the main chains (helices) are arranged in highly regular layers, while the space between layers is filled by the alkyl side chains. The molecular structure of the inter-layer region is found to be very approximately liquid-like. The simulations are also able to predict the anomalous (densification) behavior of the PAALAs as the temperature is raised through the transition value.