Probing the Flexibility of Large Conformational Changes in Protein Structures through Local Perturbations

Protein conformational changes and dynamic behavior are fundamental for such processes as catalysis, regulation, and substrate recognition. Although protein dynamics have been successfully explored in computer simulation, there is an intermediate-scale of motions that has proven difficult to simulate—the motion of individual segments or domains that move independently of the body the protein. Here, we introduce a molecular-dynamics perturbation method, the Rotamerically Induced Perturbation (RIP), which can generate large, coherent motions of structural elements in picoseconds by applying large torsional perturbations to individual sidechains. Despite the large-scale motions, secondary structure elements remain intact without the need for applying backbone positional restraints. Owing to its computational efficiency, RIP can be applied to every residue in a protein, producing a global map of deformability. This map is remarkably sparse, with the dominant sites of deformation generally found on the protein surface. The global map can be used to identify loops and helices that are less tightly bound to the protein and thus are likely sites of dynamic modulation that may have important functional consequences. Additionally, they identify individual residues that have the potential to drive large-scale coherent conformational change. Applying RIP to two well-studied proteins, Dihdydrofolate Reductase and Triosephosphate Isomerase, which possess functionally-relevant mobile loops that fluctuate on the microsecond/millisecond timescale, the RIP deformation map identifies and recapitulates the flexibility of these elements. In contrast, the RIP deformation map of α-lytic protease, a kinetically stable protein, results in a map with no significant deformations. In the N-terminal domain of HSP90, the RIP deformation map clearly identifies the ligand-binding lid as a highly flexible region capable of large conformational changes. In the Estrogen Receptor ligand-binding domain, the RIP deformation map is quite sparse except for one large conformational change involving Helix-12, which is the structural element that allosterically links ligand binding to receptor activation. RIP analysis has the potential to discover sites of functional conformational changes and the linchpin residues critical in determining these conformational states

Decrease in evaporation over the Indian monsoon region: Implication on regional hydrological cycle

Using surface observations from 58 widely distributed stations over India, a highly significant (99.9 ) decreasing trend of pan evaporation (Epan) of 9.24 mm/a/a is calculated for 1971 to 2010. This constitutes a ~10 reduction of Epan over the last four decades. While Epan is decreasing during the wet summer monsoon season (JJAS), as well as during the dry rest of the year, the rate of decrease during the dry season is much larger than that during the wet season. Apart from increasing solar dimming, surface winds are also persistently decreasing over the Indian sub-continent at the rate of -0.02 m/s/a resulting in ~40 reduction over the last four decades. Based on PenPan model, it is shown that both the above factors contribute significantly to the decreasing trend in Epan. On a continental scale, annual mean potential evaporation (Ep) is larger than rainfall (P or Ep-P > 0, moisture divergence) indicating that India is water-limited. However, during wet monsoon P > Ep (or Ep-P < 0, moisture convergence) indicating that India is energy-limited during this season. Long term data shows that annually Ep-P follows a significant decreasing trend indicating that water limitation is decreasing with time. This is largely due to stronger decreasing trend of Ep-P during the dry season compared to weaker increasing trend of Ep-P during the wet monsoon season. The scatter plot of Ep-P versus Ep also conveys that the decrease in Ep leads to increase in moisture convergence in wet season and decrease in moisture divergence in dry season

Pigeons home faster through polluted air

Air pollution, especially haze pollution, is creating health issues for both humans and other animals. However, remarkably little is known about how animals behaviourally respond to air pollution. We used multiple linear regression to analyse 415 pigeon races in the North China Plain, an area with considerable air pollution, and found that while the proportion of pigeons successfully homed was not influenced by air pollution, pigeons homed faster when the air was especially polluted. Our results may be explained by an enhanced homing motivation and possibly an enriched olfactory environment that facilitates homing. Our study provides a unique example of animals’ response to haze pollution; future studies are needed to identify proposed mechanisms underlying this effect