Parameterization of a coarse-grained model of cholesterol with point-dipole electrostatics

© 2018, Springer Nature Switzerland AG. We present a new coarse-grained (CG) model of cholesterol (CHOL) for the electrostatic-based ELBA force field. A distinguishing feature of our CHOL model is that the electrostatics is modeled by an explicit point dipole which interacts through an ideal vacuum permittivity. The CHOL model parameters were optimized in a systematic fashion, reproducing the electrostatic and nonpolar partitioning free energies of CHOL in lipid/water mixtures predicted by full-detailed atomistic molecular dynamics simulations. The CHOL model has been validated by comparison to structural, dynamic and thermodynamic properties with experimental and atomistic simulation reference data. The simulation of binary DPPC/cholesterol mixtures covering the relevant biological content of CHOL in mammalian membranes is shown to correctly predict the main lipid behavior as observed experimentally

Intentionality, Cognitive Integration and the Continuity Thesis

Naturalistic philosophers ought to think that the mind is continuous with the rest of the world and should not, therefore, be surprised by the findings of the extended mind, cognitive integration and enactivism. Not everyone is convinced that all mental phenomena are continuous with the rest of the world. For example, intentionality is often formulated in a way that makes the mind discontinuous with the rest of the world. This is a consequence of Brentano’s formulation of intentionality, I suggest, and can be overcome by revealing that the concept of intentional directedness as he receives it from the Scholastics is quite consistent with the continuity thesis. It is only when intentional directedness is conjoined with intentional inexistence that intentionality and content are consistent with a discontinuity thesis (such as Brentano’s thesis). This makes room to develop an account of intentional directedness that is consistent with the continuity thesis in the form of Peirce’s representational principle. I also argue against a form of the discontinuity thesis in the guise of the derived/underived content distinction. Having shown that intentionality is consistent with the continuity thesis I argue that we should focus on intentionality and representation as bodily enacted. I conclude that we would be better off focussing on representation and intentionality in action rather than giving abstract functional accounts of extended cognition