Development, Validation, and Applications of Nonbonded Interaction Parameters between Coarse-Grained Amino Acid and Water Models.

Interactions between amino acids and water play an important role in determining the stability and folding/unfolding, in aqueous solution, of many biological macromolecules, which affects their function. Thus, understanding the molecular-level interactions between water and amino acids is crucial to tune their function in aqueous solutions. Herein, we have developed nonbonded interaction parameters between the coarse-grained (CG) models of 20 amino acids and the one-site CG water model. The nonbonded parameters, represented using the 12-6 Lennard Jones (LJ) potential form, have been optimized using an artificial neural network (ANN)-assisted particle swarm optimization (PSO) (ANN-assisted PSO) method. All-atom (AA) molecular dynamics (MD) simulations of dipeptides in TIP3P water molecules were performed to calculate the Gibbs hydration free energies. The nonbonded force-field (FF) parameters between CG amino acids and the one-site CG water model were developed to accurately reproduce these energies. Furthermore, to test the transferability of these newly developed parameters, we calculated the hydration free energies of the analogues of the amino acid side chains, which showed good agreement with reported experimental data. Additionally, we show the applicability of these models by performing self-assembly simulations of peptide amphiphiles. Overall, these models are transferable and can be used to study the self-assembly of various biomaterials and biomolecules to develop a mechanistic understanding of these processes.

Gene expression profiling of liver X receptor α and Bcl-2-associated X protein in experimental transection spinal cord-injured rats.

BACKGROUND: Study of molecular responses to central nervous system injury would be helpful for controlling the harmful pathways post-injury and triggering the useful pathways required for the treatment of injury. OBJECTIVE: To investigate the expression level of liver X receptor α (LXRα) which has anti-inflammatory effects and pro-apoptotic Bcl-2-associated X protein (Bax) upon spinal cord injury (SCI). DESIGN: To induce SCI, transection was carried out at T9 level of male Wister rats. Approximately 8 mm of rostral, caudal, and epicenter tissues of injured sites in treated rats were chosen for quantitative real-time polymerase chain reaction at the 6, 24, and 72 hours, and 7 and 10 days post-surgery. RESULTS: Our results showed a complicated temporal and spatial pattern of alteration in LXRα and Bax mRNA expression levels after SCI. LXRα expression level followed a homologues pattern (additive and subtractive wave) with a difference in time at three areas of studied. Rostral, caudal, and epicenter expression patterns of Bax were dissimilar in these areas. Gradual increase in the expression of Bax without any decrease at the rostral area was observed, presumably indicating the active transcription process of this gene, regardless of its protein situation. CONCLUSION: A time lapse significant change in Bax expression level was observed only in the epicenter of injury, emphasizing that apoptotic responses are limited to this area. Furthermore, an increase in LXRα transcription level was observed first in rostral area and then extended to epicentral and caudal areas, implying that inflammation responses extended from rostral to caudal areas.