Coarse-grained model of entropic allostery

Many signaling functions in molecular biology require proteins to bind to substrates such as DNA in response to environmental signals such as the simultaneous binding to a small molecule. Examples are repressor proteins which may transmit information via a conformational change in response to the ligand binding. An alternative entropic mechanism of "allostery" suggests that the inducer ligand changes the intramolecular vibrational entropy, not just the mean static structure. We present a quantitative, coarse-grained model of entropic allostery, which suggests design rules for internal cohesive potentials in proteins employing this effect. It also addresses the issue of how the signal information to bind or unbind is transmitted through the protein. The model may be applicable to a wide range of repressors and also to signaling in trans-membrane proteins

Kramers rate theory of ionization and dissociation of bound states

Calculating the microscopic dissociation rate of a bound state, such as a classical diatomic molecule, has been difficult so far. The problem was that standard theories require an energy barrier over which the bound particle (or state) escapes into the preferred low-energy state. This is not the case when the long-range repulsion responsible for the barrier is either absent or screened (as in Cooper pairs, ionized plasma, or biomolecular complexes). We solve this classical problem by accounting for entropic memory at the microscopic level. The theory predicts dissociation rates for arbitrary potentials and is successfully tested on the example of plasma, where it yields an estimate of ionization in the core of Sun in excellent agreement with experiments. In biology, the new theory accounts for crowding in receptor-ligand kinetics and protein aggregation

Spinodal-assisted crystallization in polymer melts

Recent experiments in some polymer melts quenched below the melting temperature have reported spinodal kinetics in small-angle x-ray scattering before the emergence of a crystalline structure. To explain these observations we propose that the coupling between density and chain conformation induces a liquid-liquid binodal within the equilibrium liquid-crystalline solid coexistence region. A simple phenomenological theory is developed to illustrate this idea, and several experimentally testable consequences are discussed. Shear is shown to enhance the kinetic role of the hidden binodal

Parallel Excluded Volume Tempering for Polymer Melts

We have developed a technique to accelerate the acquisition of effectively uncorrelated configurations for off-lattice models of dense polymer melts which makes use of both parallel tempering and large scale Monte Carlo moves. The method is based upon simulating a set of systems in parallel, each of which has a slightly different repulsive core potential, such that a thermodynamic path from full excluded volume to an ideal gas of random walks is generated. While each system is run with standard stochastic dynamics, resulting in an NVT ensemble, we implement the parallel tempering through stochastic swaps between the configurations of adjacent potentials, and the large scale Monte Carlo moves through attempted pivot and translation moves which reach a realistic acceptance probability as the limit of the ideal gas of random walks is approached. Compared to pure stochastic dynamics, this results in an increased efficiency even for a system of chains as short as $N = 60$ monomers, however at this chain length the large scale Monte Carlo moves were ineffective. For even longer chains the speedup becomes substantial, as observed from preliminary data for $N = 200$

Mothers’ accounts of the impact on emotional wellbeing of organised peer support in pregnancy and early parenthood: a qualitative study

Background The transition to parenthood is a potentially vulnerable time for mothers’ mental health and approximately 9–21% of women experience depression and/or anxiety at this time. Many more experience sub-clinical symptoms of depression and anxiety, as well as stress, low self-esteem and a loss of confidence. Women’s emotional wellbeing is more at risk if they have little social support, a low income, are single parents or have a poor relationship with their partner. Peer support can comprise emotional, affirmational, informational and practical support; evidence of its impact on emotional wellbeing during pregnancy and afterwards is mixed. Methods This was a descriptive qualitative study, informed by phenomenological social psychology, exploring women’s experiences of the impact of organised peer support on their emotional wellbeing during pregnancy and in early parenthood. Semi-structured qualitative interviews were undertaken with women who had received peer support provided by ten projects in different parts of England, including both projects offering ‘mental health’ peer support and others offering more broadly-based peer support. The majority of participants were disadvantaged Black and ethnic minority women, including recent migrants. Interviews were audio-recorded and transcripts were analysed using inductive thematic analysis. Results 47 mothers were interviewed. Two key themes emerged: (1) ‘mothers’ self-identified emotional needs’, containing the subthemes ‘emotional distress’, ‘stressful circumstances’, ‘lack of social support’, and ‘unwilling to be open with professionals’; and (2) ‘how peer support affects mothers’, containing the subthemes ‘social connection’, ‘being heard’, ‘building confidence’, ‘empowerment’, ‘feeling valued’, ‘reducing stress through practical support’ and ‘the significance of “mental health” peer experiences’. Women described how peer support contributed to reducing their low mood and anxiety by overcoming feelings of isolation, disempowerment and stress, and increasing feelings of self-esteem, self-efficacy and parenting competence. Conclusion One-to-one peer support during pregnancy and after birth can have a number of interrelated positive impacts on the emotional wellbeing of mothers. Peer support is a promising and valued intervention, and may have particular salience for ethnic minority women, those who are recent migrants and women experiencing multiple disadvantages

Phase Separation of Rigid-Rod Suspensions in Shear Flow

We analyze the behavior of a suspension of rigid rod-like particles in shear flow using a modified version of the Doi model, and construct diagrams for phase coexistence under conditions of constant imposed stress and constant imposed strain rate, among paranematic, flow-aligning nematic, and log-rolling nematic states. We calculate the effective constitutive relations that would be measured through the regime of phase separation into shear bands. We calculate phase coexistence by examining the stability of interfacial steady states and find a wide range of possible ``phase'' behaviors.Comment: 23 pages 19 figures, revised version to be published in Physical Review